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NERVE PHYSIOLOGY
DR SARAN AJAY
DEPT OF PHYSIOLOGY, GMCM
DEPT OF PHYSIOLOGY, GMCM 10
What is an excitable tissue?
Excitable Tissue
• Property of responding to a stimulus is called
excitability or irritability
• A sudden and appreciable change in environment
of living matter, lasting for a minimum time
constitute a stimulus
• Capable of generation of electrical impulses at
their membranes
• These impulses are used to transmit signals along the
membranes
• Mainly 2 excitable tissues – Nerve & muscle
DEPT OF PHYSIOLOGY, GMCM 12
• Nerves - specialized for function of reception,
integration and transmission of information in the body
• Muscles - also excitable tissues but are characterized
by mechanical contraction
DEPT OF PHYSIOLOGY, GMCM 13
DEPT OF PHYSIOLOGY, GMCM 14
CNS : Central Nervous System
PNS : Peripheral Nervous System
NERVOUS SYSTEM
Cellular elements of CNS
• Neurons - basic building blocks
• 1011 neurons
• Also contain Glial cells
• 40% of human genes participate in the formation of CNS
DEPT OF PHYSIOLOGY, GMCM 16
DEPT OF PHYSIOLOGY, GMCM 19
STRUCTURE
OF NEURON
DEPT OF PHYSIOLOGY, GMCM 20
Cell body/ Soma/ Perikaryon
1. Round , stellate, pyramidal, fusiform
2. Nucleus with nucleoli
3. No centrosome
4. Cytoplasm – mitochondria, ER, Golgi apparatus, Nissl
granules
5. Nissl granules
• Basophilic granules
• Contains rough ER
• Involved in protein synthesis
• Absent from axon & axon hillock
• Chromatolysis - disintegrate and finally disappear
DEPT OF PHYSIOLOGY, GMCM 22
7. Neurofibrils
• Microfilaments and Microtubules
• Alzheimer's disease: microfilament proteins →
neurofibrillary tangles
DEPT OF PHYSIOLOGY, GMCM 24
DEPT OF PHYSIOLOGY, GMCM 25
DEPT OF PHYSIOLOGY, GMCM 26
8. Pigment granules
• Neuromelanin- in substantia nigra
• Lipofuscin- aging neurons
DEPT OF PHYSIOLOGY, GMCM 28
Site of cell bodies
• Gray matter of CNS
• Autonomic and posterior nerve root ganglia
Group of cell bodies
• Inside the CNS- Nucleus
• Outside CNS- Ganglia
DEPT OF PHYSIOLOGY, GMCM 30
Dendrites
• Small multiple branched processes
• Short course, irregular number
• Contains Nissl bodies
• Thorny projections – Dendritic spines
• Impulses travel towards the cell body
DEPT OF PHYSIOLOGY, GMCM 31
Axon
• Single long process
• Arise from Axon hillock
• Initial segment – first part of axon
• Axolemma and axoplasm
DEPT OF PHYSIOLOGY, GMCM 34
DEPT OF PHYSIOLOGY, GMCM 35
• Axon divides into presynaptic terminals, which end in
• Synaptic knobs/ terminal buttons/ axon telodendrion
• Carries impulses away from cell body
• Myelinated and unmyelinated nerve fibers
DEPT OF PHYSIOLOGY, GMCM 36
DEPT OF PHYSIOLOGY, GMCM 39
MYELINATION
DEPT OF PHYSIOLOGY, GMCM 40
Myelination in PNS
DEPT OF PHYSIOLOGY, GMCM 41
• Schwann cell - wraps its membrane around an axon up to
100 times
• Axons invaginate into cytoplasm of Schwann cell
• So becomes suspended in a fold of Schwann cell
membrane - mesaxon
DEPT OF PHYSIOLOGY, GMCM 42
DEPT OF PHYSIOLOGY, GMCM 44
• Lipids are deposited between the layers of Schwann cell
• Compacted to form myelin sheath – by Protein zero( P0)
• Extracellular portions of this membrane proteins on the
apposing membranes lock to each other
• Mutations in the gene for P0 → Peripheral neuropathy
• Outermost cell membrane → Neurilemma
DEPT OF PHYSIOLOGY, GMCM 46
DEPT OF PHYSIOLOGY, GMCM 47
• Each Schwann cell provide myelin sheath for a short
segment of axon
• Between 2 segments - 1µm constrictions – Nodes of
Ranvier
• Myelin is absent at axonal endings
DEPT OF PHYSIOLOGY, GMCM 48
Functions of Myelin
1. Increases velocity of conduction: Saltatory conduction
2. Reduces energy expenditure for conduction
3. Acts as an insulator – prevents cross stimulation
DEPT OF PHYSIOLOGY, GMCM 50
DEPT OF PHYSIOLOGY, GMCM 51
In unmyelinated nerves,
• Axon is surrounded by Schwann cell without wrapping of
membrane
DEPT OF PHYSIOLOGY, GMCM 52
Myelination in CNS
• Oligodendrocytes form myelin
• They extend multiple processes and form myelin on many
axons
DEPT OF PHYSIOLOGY, GMCM 53
DEPT OF PHYSIOLOGY, GMCM 54
Myelinogenesis
• Begins at 4th month of intra uterine life
• Sensory fibers – 4th-5th month
• Pyramidal tract (motor fibers) – 2 years
DEPT OF PHYSIOLOGY, GMCM 55
1. Babinski Test in children – Extensor Response
2. Mutations in gene for Protein0 → Peripheral
neuropathies
DEPT OF PHYSIOLOGY, GMCM 56
Applied Aspects
2. Multiple sclerosis - demyelinating disease
• Autoimmune
• Antibodies and WBCs attack myelin →
inflammation & injury to the sheath → eventually
the nerves are affected
DEPT OF PHYSIOLOGY, GMCM 58
• Loss of myelin → leakage of K+ through voltage-gated
channels → hyperpolarization → failure to conduct
impulses
• Nerve conduction tests show slowed conduction in motor
& sensory pathways
• Numbness and weakness
• Optic neuritis
DEPT OF PHYSIOLOGY, GMCM 60
NERVE PHYSIOLOGY- 2
DR SARAN AJAY
DEPT OF PHYSIOLOGY, GMCM
Specific Learning Objectives
• Functional Zones of a Neuron
• Classification of Neuron
• Transport and Metabolism
• Peripheral Nerve
• Nerve Injury and Degeneration
• Neuroglia
• Neurotropins
DEPT OF PHYSIOLOGY, GMCM 8
FUNCTIONAL
ZONES OF
A NEURON
DEPT OF PHYSIOLOGY, GMCM 9
Functional Zones of a Neuron
1. Receptor zone- dendritic zone- local potentials
2. Site of origin of conducted impulses
• Motor neuron – initial segment
• Sensory – 1st node of Ranvier
3. Zone of all or none transmission- axon
4. Zone of secretion of neurotransmitters
DEPT OF PHYSIOLOGY, GMCM 10
Granules or vesicles – neurotransmitter
Termination
• Synapse
• Effecter organ (muscle or gland)
• Peripheral ganglion
DEPT OF PHYSIOLOGY, GMCM 11
CLASSIFICATION
OF NEURONS
Classification of neuron
1. Depending upon number of poles/ structural classification
2. Depending upon the function
3. Depending upon length of axon
DEPT OF PHYSIOLOGY, GMCM 15
A. Depending upon number of poles
1. Unipolar neuron
• Single pole
• Both dendrites and axon arise from that
DEPT OF PHYSIOLOGY, GMCM 16
DEPT OF PHYSIOLOGY, GMCM 17
2. Bipolar neuron
2 poles- one for axon, one for dendrite
3. Pseudo unipolar neuron
• A subclass of bipolar cells
• A single process splits into two, both of which function as axons
• Peripheral one going to skin or muscle and central one to spinal
cord
• Eg: Dorsal root ganglion (DRG)
DEPT OF PHYSIOLOGY, GMCM 18
DEPT OF PHYSIOLOGY, GMCM 19
4. Multi polar neuron
• One pole- axon
• Other poles- dendrites
DEPT OF PHYSIOLOGY, GMCM 20
Q. KUHS AUGUST 2015
DEPT OF PHYSIOLOGY, GMCM 21
B. Depending on function
1. Sensory /afferent neuron
2. Motor / efferent neuron
3. Interneuron
DEPT OF PHYSIOLOGY, GMCM 22
C. Depending upon length of axon
Golgi type 1- also known as projection neurons
• Have long axons
• Neurons forming peripheral nerves & long tracts of brain
Golgi type 2- short circuit neuron
• Short axons
• Numerous in cerebral cortex, cerebellar cortex, retina
DEPT OF PHYSIOLOGY, GMCM 24
Biological activities in a neuron
• Protein synthesis & transport
• Metabolism
• Excitation and conduction of impulses
Protein synthesis & Transport
• Soma is the machinery for protein synthesis
• Neurotransmitters and other proteins that are needed at the
axon terminals
• Transport of proteins and polypeptides to axonal ending
occurs by axoplasmic flow
Axoplasmic flow/ transport
1. Anterograde transport: from cell body → axon terminal
• Fast axonal transport- 400 mm/day
• Slow axonal transport- 0.5-10 mm/day
• Occurs along microtubules
• Requires 2 molecular motors
Dynein & Kinesin
Substances transported are
• Fast Axonal transport
1. Mitochondria and other membrane bound organelles
2. Small Vesicles
3. Actin and Myosin
• Slow Axonal Transport
1. Tubulins of microtubules
2. Protein subunits of neurofilaments
2. Retrograde transport
• From axon terminal → cell body
• 200mm/ day
• Occurs along microtubules
Substances transported are
1. Used synaptic vesicles,
2. Nerve growth factors (NGF)
3. Viruses like polio, herpes simplex and rabies
4. Toxins e.g.: tetanus toxin
Metabolism
• Low level
• 70% total energy is used to maintain the polarity of membrane
• By action of Na+- K+ ATPase
• At maximum activity– metabolic rate doubles
Peripheral Nerve
• Compact bundle of axons located outside CNS – Nerve
• Axons are arranged in different bundles – Fasciculi
• Each axon is covered by Endoneurium
• Each fasciculus is covered by Perineurium
• Whole nerve is covered by Epineurium
NERVE INJURY -
DEGENERATION
REGENERATION
Response to injury
Types of injury
• Cut injury
• Crush injury
• Ischemia
• Injection of toxic substance
• Diseases like DM, syphilis
• Pressure on the nerve
A. Physical and chemical degenerative changes
1. Axon distal to the injury (anterograde degeneration)
2. Proximal to the injury
3. Cell body
(retrograde degeneration)
1. Anterograde degeneration (Wallerian)
• Axon distal to the injury
• Augustus Waller
Q. KUHS 2022 JULY
a) Changes in impulse conduction
b) Changes in the axon
c) Changes in the myelin sheath
d) Changes in the Neurilemma – Ghost tube
a. Changes in impulse conduction
1. If severed - stops within hours
2. If crushed
• Up to 3 days normal conduction
• After 3 days deteriorates seriously
• After 5 days no impulse evoked
b. Changes in Axon
1. Swells up
2. Irregular in shape
3. Breaks into small fragments
4. Axon terminals retract from post synaptic target
5. Within several weeks axon and its terminals degenerate
c. Myelin Sheath
1. Small fragments
2. Hydrolysis of myelin to fatty droplets
3. Begins by 8th day and completed by 32 days
d. Neurilemma
1. Intact
2. Schwann cells – increase size and multiply
3. Macrophages remove degenerating axons, myelin
and cellular debris
4. Neurilemmal tube becomes empty – Ghost tube
2. Retrograde degeneration
• Proximal to injury
• Similar to changes seen in distal part of axon
• Occurs only up to first or second node of Ranvier
• Changes seen in proximal part of axon along with those
in cell body constitute retrograde degeneration
3. Changes in cell body
• Starts within 48hr → continues up to 15-20 days
• Cell organelles are fragmented and eventually disappear
• Cell body draws in more fluid, swells up
• Nissl substances undergo Chromatolysis
• Nucleus is displaced to periphery and extruded out of cell
B. Regeneration
Under favorable conditions
• Neurilemma present
• Cell body & nucleus are intact
• Gap less than 3mm
• Sliced cut, cut ends in straight line
• Starts within 4 days of injury
• More active after 30 days
• Complete recovery- several months to one year
• 1 – 4 mm per day
Changes in the axon
• From proximal stump axon elongates and give out fibrils
• Schwann cells of distal end guide the fibril to enter the endo
neural tube
• Fibril makes contact with the peripheral end organ
• Myelination – completed in 1 year
• 80% of original diameter is regained
Changes in the cell body
• 20-80d
• Nissl granules followed by Golgi apparatus appear in
cell body
• Cell loses excess water, regains its normal size
• Nucleus occupies the central position
Complication following nerve injury
1. Complete atrophy
2. Functional complications- misinterpretation of
sensations
3. Neuroma formation- if fibrils could not find distal cut
end, it will form a mass
4. Phantom Limb
• Feeling perceived by a patient after amputation of limb
• Neuroma when stimulated, patient feel the lost limb
Phantom Limb / Pain
NERVE PHYSIOLOGY- 2b
DR SARAN AJAY
DEPT OF PHYSIOLOGY, GMCM
Specific Learning Objectives
• Functional Zones of a Neuron
• Classification of Neuron
• Transport and Metabolism
• Peripheral Nerve
• Nerve Injury and Degeneration
• Neuroglia
• Neurotropins
Glial cells/ Neuroglia
• Supporting cells in nervous system
• 2 types: Microglia & Macroglia
• Microglia arise from macrophages
• Act as scavenger cells – remove debris resulting from
injury, infection, and diseases
• Macroglia: Oligodendrocytes, Schwann cells, & Astrocytes
• Oligodendrocytes
• In white matter provide myelin
• In gray matter support neurons
• Schwann cells provide myelin to PNS
• Astrocytes most common glia in the CNS, star like shape
Astrocytes
Astrocytes help to regulate the microenvironment in CNS
under normal conditions and also in response to damage.
• Fibrous
• contain intermediate filaments
• found in white matter
• Protoplasmic – found in gray matter
Functions
• Astrocytes send processes to blood vessels → induce
capillaries to form tight junctions → Blood–brain barrier
• Also send processes that envelop synapses and surface
of nerve cells
• Produce neurotropins
• Help to maintain concentration of ions and neurotransmitters
• Regulate microenvironment of neuron
• Membrane potential of protoplasmic astrocyte varies with
external K+
Specific Learning Objectives
• Functional Zones of a Neuron
• Classification of Neuron
• Transport and Metabolism
• Peripheral Nerve
• Nerve Injury and Degeneration
• Neuroglia
• Neurotropins
Neurotrophins
• Proteins necessary for survival and growth of neurons
• Site of production- muscles, structures innervated by
neuron, astrocytes, neurons
• Retrograde transport and Anterograde transport
Nerve growth factor (NGF)
• First neurotrophin identified
• Sympathetic nerves, sensory nerves
• Trk A Receptor
Brain derived neurotrophic factor (BDNF)
• Trk B
• Peripheral sensory nerves
Neurotrophin -3
• Trk B and Trk C
• Cutaneous mechanoreceptors
• Proprioceptor neurons that innervate muscle spindle
Specific Learning Objectives
• Functional Zones of a Neuron
• Classification of Neuron
• Transport and Metabolism
• Peripheral Nerve
• Nerve Injury and Degeneration
• Neuroglia
• Neurotropins
NERVE PHYSIOLOGY- 3
DR SARAN AJAY
DEPT. OF PHYSIOLOGY, GMCM
Hodgkin and Huxley
Nobel Prize in Physiology
and Medicine 1963
Specific Learning Objectives
• Membrane Potential
• Resting Membrane Potential
• Genesis of RMP
• Electrotonic Potentials
DEPT. OF PHYSIOLOGY, GMCM 7
MEMBRANE
POTENTIAL
DEPT. OF PHYSIOLOGY, GMCM 8
• The potential difference across the membrane of all living
cells
• Results from the separation of charges across the cell
membrane
DEPT. OF PHYSIOLOGY, GMCM 9
+
DEPT. OF PHYSIOLOGY, GMCM 10
DEPT. OF PHYSIOLOGY, GMCM 11
DEPT. OF PHYSIOLOGY, GMCM 12
• Note that the membrane itself is not charged.
• The term membrane potential refers to the difference in charge
between the wafer-thin regions of ICF and ECF lying next to the
inside and outside of the membrane, respectively.
DEPT. OF PHYSIOLOGY, GMCM 13
DEPT. OF PHYSIOLOGY, GMCM 14
1. Transport processes
2. Signaling purposes
DEPT. OF PHYSIOLOGY, GMCM 16
• The energy stored in this miniature battery can drive a variety of
transmembrane transport processes.
• Electrically excitable cells such as brain neurons and heart
myocytes also use this energy for signalling purposes. The brief
electrical impulses produced by such cells are called action
potentials.
DEPT. OF PHYSIOLOGY, GMCM 17
More the separation of charges, more is the membrane potential.
DEPT. OF PHYSIOLOGY, GMCM 18
• The inside is negative with respect to the outside
• Varies from cell to cell
• Varies with functional status
DEPT. OF PHYSIOLOGY, GMCM 19
• The cells of excitable tissues—namely, nerve cells and muscle
cells—have the ability to produce rapid, transient changes in their
membrane potential when excited.
• These brief fluctuations in potential serve as electrical signals or
action potentials.
DEPT. OF PHYSIOLOGY, GMCM 20
Specific Learning Objectives
• Membrane Potential
• Resting Membrane Potential
• Genesis of RMP
• Electrotonic Potentials
DEPT. OF PHYSIOLOGY, GMCM 22
• It is the potential difference across the membrane while the
cell is at rest.
Neuron : - 70mV
Skeletal & cardiac muscle : - 90mV
RBC : - 10mV
• Transmembrane / Steady state potential / Diffusion potential
Resting Membrane Potential
DEPT. OF PHYSIOLOGY, GMCM 23
• The constant membrane potential present in the cells of non excitable
tissues and those of excitable tissues when they are at rest—that is,
when they are not producing electrical signals—is known as the
resting membrane potential.
DEPT. OF PHYSIOLOGY, GMCM 24
Recording of RMP
DEPT. OF PHYSIOLOGY, GMCM 25
• Microelectrodes
• Amplifier
• Voltmeter
• Cathode Ray Oscilloscope (CRO) for rapid changes
Equipment
DEPT. OF PHYSIOLOGY, GMCM 26
Specific Learning Objectives
• Membrane Potential
• Resting Membrane Potential
• Genesis of RMP
• Electrotonic Potentials
DEPT. OF PHYSIOLOGY, GMCM 28
Genesis of RMP
• Due to the unequal distribution of ions across the cell
membrane (concentration gradient)
• Their selective movement through the cell membrane
DEPT. OF PHYSIOLOGY, GMCM 29
The ions primarily responsible for RMP
1. Na+
2. K+
3. A-
A- = Large, negatively charged (anionic) intracellular proteins
DEPT. OF PHYSIOLOGY, GMCM 30
FACTORS involved
in Genesis of RMP
5
DEPT. OF PHYSIOLOGY, GMCM 31
“The phenomenon of predictable and unequal
distribution of permeant charged ions on either
side of a semipermeable membrane, in the presence
of impermeant charged ions”
1. The Gibbs-Donnan effect
DEPT. OF PHYSIOLOGY, GMCM 33
DEPT. OF PHYSIOLOGY, GMCM 34
DEPT. OF PHYSIOLOGY, GMCM 36
Non
permeable
anion
DEPT. OF PHYSIOLOGY, GMCM 38
DEPT. OF PHYSIOLOGY, GMCM 39
DEPT. OF PHYSIOLOGY, GMCM 40
“The phenomenon of predictable and unequal
distribution of permeant charged ions on either
side of a semipermeable membrane, in the presence
of impermeant charged ions”
The Gibbs-Donnan effect
DEPT. OF PHYSIOLOGY, GMCM 41
When 2 ionized solutions are separated by a semi- permeable
membrane, at equilibrium
1. Each solution will be electrically neutral
2. (Diffusible cations)A X (Diffusible anions)A =
(Diffusible cations)B X (Diffusible anions)B
DEPT. OF PHYSIOLOGY, GMCM 43
• Diffusible cations (K+) more on the side of non-diffusible
anions (proteins) : ICF
• Less diffusible cations (Na+) more on the side of diffusible
anions (Cl-) : ECF
DEPT. OF PHYSIOLOGY, GMCM 44
Na+, Cl-
K+
K+ , anions
Na+ ,Cl-
ECF
ICF
DEPT. OF PHYSIOLOGY, GMCM 45
Ions ECF mmol/L ICF mmol/L
Na+ 150 15
K+ 5.5 150
Cl- 125 9
Proteins 0 65
Distribution of ions
DEPT. OF PHYSIOLOGY, GMCM 46
2. Selective Permeability of the cell membrane
• Separates ECF & ICF
DEPT. OF PHYSIOLOGY, GMCM 47
• Cytoplasm has diffusible & non-diffusible ions
• Membrane is freely permeable to K+ and Cl-
• Moderately permeable to Na+
• Impermeable to intracellular proteins and organic
phosphates (negatively charged ions)
DEPT. OF PHYSIOLOGY, GMCM 48
Permeability to K+
• Potassium sodium leak channels
• About 50-100 times than that for
Na+
• Hydrated K+ ion is smaller
DEPT. OF PHYSIOLOGY, GMCM 49
• K+ efflux - not compensated by Na influx
• K+ efflux is not accompanied by negatively charged
anions
• More negative ions remain inside the cell → creates
negativity inside the cell
DEPT. OF PHYSIOLOGY, GMCM 50
Asymmetric distribution of ions
↓
Concentration & Electrical gradients
↓
Diffusion
DEPT. OF PHYSIOLOGY, GMCM 52
K+ as the only diffusible ion
DEPT. OF PHYSIOLOGY, GMCM 54
DEPT. OF PHYSIOLOGY, GMCM 55
ECF 5.5 mmol/L of H2O
ICF 150 mmol/L of H2O
C
G
E
G
DEPT. OF PHYSIOLOGY, GMCM 56
• Equilibrium is reached
• Driving forces down conc. & electrical gradients are
equal and opposite
• No net movement
DEPT. OF PHYSIOLOGY, GMCM 57
3. Nernst Equation
DEPT. OF PHYSIOLOGY, GMCM 59
Nernst potential/ Equilibrium potential for K+
Ek = -61.5 log [Ki
+ ] = - 90mV (37 degC)
[Ko
+]
[Ko
+] = K+ concentration outside the cell
[Ki
+] = K+ concentration inside the cell
DEPT. OF PHYSIOLOGY, GMCM 60
DEPT. OF PHYSIOLOGY, GMCM 61
K+ as the only diffusible ion
DEPT. OF PHYSIOLOGY, GMCM 62
DEPT. OF PHYSIOLOGY, GMCM 63
1. Polarity/ electrical charge
2. Permeability of membrane to each
3. Concentration inside & outside
When multiple ions are involved,
Membrane potential depends on
DEPT. OF PHYSIOLOGY, GMCM 64
4. Goldman Hodgkin – Katz equation
• With this equation RMP calculated is –67 mV
DEPT. OF PHYSIOLOGY, GMCM 65
DEPT. OF PHYSIOLOGY, GMCM 66
• Greater the permeability of an ion, greater is the tendency
for that ion to drive the membrane potential towards its own
equilibrium potential
DEPT. OF PHYSIOLOGY, GMCM 67
5. Na+ - K+ ATPase
• Steady ion leaks cannot continue forever without
eventually dissipating the ion gradients
• This is prevented by the Na+-K+ ATPase
• It actively moves 3 Na+ out and 2 K+ in against their
electrochemical gradients
DEPT. OF PHYSIOLOGY, GMCM 69
Jens Skou
Nobel Prize in Physiology and Medicine 1997
DEPT. OF PHYSIOLOGY, GMCM 71
• Results in continuous loss of positive charges from inside
the membrane
• Creates an additional degree of negativity
• So it is electrogenic and contributes to RMP about – 4mV
• Helps to maintain osmotic balance.
DEPT. OF PHYSIOLOGY, GMCM 72
1. Donnan effect & Gibbs Donnan Equilibrium
2. Selective permeability of cell membrane to ions
3. Nernst Equation
4. Goldman Hodgkin Katz Equation
5. Sodium- potassium ATPase pump
Factors involved in genesis of RMP
DEPT. OF PHYSIOLOGY, GMCM 73
Factors affecting RMP
1. ECF K+ concentration
ECF K+ ↑: magnitude of RMP ↓ → neuron becomes more
excitable
2. Inhibition of Na+ K+ ATPase
3. ECF Na+: no effect
DEPT. OF PHYSIOLOGY, GMCM 74
• If the extracellular level of K + is increased (hyperkalemia), the resting
potential moves closer to the threshold for eliciting an action
potential, thus the neuron becomes more excitable.
• If the extracellular level of K + is decreased (hypokalemia), the
membrane potential is reduced and the neuron is hyperpolarized.
DEPT. OF PHYSIOLOGY, GMCM 75
NERVE PHYSIOLOGY- 4
DR SARAN AJAY
DEPT. OF PHYSIOLOGY, GMCM
Electrical Properties of a Neuron
1. Excitability
2. Conductivity
DEPT. OF PHYSIOLOGY, GMCM 3
Excitability
• Stimulus
• Types
• Strength/ intensity
Threshold stimulus
Subthreshold stimulus
Suprathreshold stimulus
DEPT. OF PHYSIOLOGY, GMCM 4
Application of stimulus will produce
1. Local non-propagated potentials
Electrotonic potentials
2. Propagated potentials
Action potential/ nerve impulse
DEPT. OF PHYSIOLOGY, GMCM 5
Specific Learning Objectives
• Electrotonic Potential
• Action Potential
• Ionic Basis of Action Potential
• Graded Potential v/s Action Potential
Electrotonic Potentials
ELECTROTONIC
POTENTIALS
DEPT. OF PHYSIOLOGY, GMCM 11
• Demonstrated by placing recording electrodes within a
few millimeters of a stimulating electrode
• Applying subthreshold stimuli of fixed duration
DEPT. OF PHYSIOLOGY, GMCM 12
Recording of electrotonic potential
Subthreshold
Stimulus
• Leads to a localized potential change
• Rises sharply and decays exponentially with time
• Graded response can be produced both at cathode and
anode
1. Catelectrotonic potential
2. Anelectrotonic potential
DEPT. OF PHYSIOLOGY, GMCM 14
DEPT. OF PHYSIOLOGY, GMCM 15
DEPT. OF PHYSIOLOGY, GMCM 17
Graded Potential – Examples
1. End plate potential
2. Post synaptic potential
3. Generator or receptor potential
DEPT. OF PHYSIOLOGY, GMCM 18
Specific Learning Objectives
• Electrotonic Potential
• Action Potential
• Ionic Basis of Action Potential
• Graded Potential v/s Action Potential
ACTION
POTENTIAL
• Brief, rapid, large depolarizing changes in membrane
potential
• Transiently, resting negative potential → positive potential
• Conducted, propagated along the nerve fiber
• Non decremental fashion
• Nerve signals are transmitted by action potentials
How is an action potential recorded?
1. Stimulating Electrodes (min - threshold stimuli)
2. Recording Electrodes
3. Amplifier
4. Cathode Ray Oscilloscope
Threshold Stimuli
1. Resting stage
2. Depolarization
3. Repolarization
Stages of Action Potential
1. RMP –70mV (polarized state)
2. Stimulus artifact
3. Latent period (Isoelectric potential interval)
4. Depolarization (reverse polarization)
5. Firing level
6. Spike potential
7. After depolarization
8. After hyperpolarization
Marked changes in membrane permeability and
ion movement lead to action potential.
NERVE PHYSIOLOGY- 5
DR SARAN AJAY
DEPT. OF PHYSIOLOGY, GMCM
Specific Learning Objectives
• Ionic Basis of Action Potential
• Properties of Action Potential
• Graded Potential v/s Action Potential
• Types of Action Potential
DEPT. OF PHYSIOLOGY, GMCM 4
IONIC BASIS OF
ACTION POTENTIAL
DEPT. OF PHYSIOLOGY, GMCM 5
1. Stimulus artifact – Current leakage from stimulating
to recording electrodes
2. Latent Period – Time taken by the impulse to travel
along the axon
• Distance between electrodes
• Velocity of conduction
DEPT. OF PHYSIOLOGY, GMCM 6
3. Depolarization
Threshold stimulus
↓
Initial slow depolarization (a change of 7–15mV)
(opening of few voltage gated Na+ channels)
DEPT. OF PHYSIOLOGY, GMCM 7
Voltage Gated Sodium Channel
DEPT. OF PHYSIOLOGY, GMCM 8
Threshold stimulus
↓
Initial slow depolarization (a change of 7–15mV)
(opening of few voltage gated Na+ channels)
↓
Rapid depolarization (at –55mV) Firing Level
(opening of more and more voltage gated Na+ channels)
DEPT. OF PHYSIOLOGY, GMCM 9
Feedback Control in Voltage Gated Ion Channels / Hodgkin Cycle
DEPT. OF PHYSIOLOGY, GMCM 10
Firing Level
• At -55mV more Na channels opens → gush of Na+ into
cell (500 – 5000 fold)
DEPT. OF PHYSIOLOGY, GMCM 11
• Membrane potential moves towards equilibrium potential
for Na+ : +61 mV
• But membrane potential does not reach to +61 mV
because Na+ conductance is short lived.
DEPT. OF PHYSIOLOGY, GMCM 12
DEPT. OF PHYSIOLOGY, GMCM 13
DEPT. OF PHYSIOLOGY, GMCM 14
1. After few 10,000th of a second inactivation gate closed
→ Na+ influx ↓
• Inactivation gate will remain closed till (or near) reaching
RMP again.
4. Repolarization
DEPT. OF PHYSIOLOGY, GMCM 15
2. Direction of electrical gradient of Na+ is reversed during
overshoot
• Leads to decrease in Na+ influx
3. Opening of voltage gated K+ channel also contributes to
repolarization
DEPT. OF PHYSIOLOGY, GMCM 16
Voltage Gated Potassium Channel
DEPT. OF PHYSIOLOGY, GMCM 17
• Only 1 gate inside, resting state gate is closed
• As membrane potential rises -70 to 0 → slow
conformational change in the K+ gate occurs →
opening of gate
• So repolarization is due to both ↑ K+ efflux and ↓ Na+
influx
DEPT. OF PHYSIOLOGY, GMCM 18
Feedback Control in Voltage Gated Ion Channels
DEPT. OF PHYSIOLOGY, GMCM 19
DEPT. OF PHYSIOLOGY, GMCM 20
DEPT. OF PHYSIOLOGY, GMCM 21
5. After depolarization due to slowing of K+ efflux
6. After hyperpolarization due to slow return of K+
channel to closed state
DEPT. OF PHYSIOLOGY, GMCM 22
7. Re-establishing Na+ and K+ ionic gradients
• Transmission of action potential slightly reduces
concentration differences of Na+ and K+ inside and
outside the membrane
DEPT. OF PHYSIOLOGY, GMCM 23
• Achieved by action of the Na+ - K+ pump
• This pump requires energy derived from ATP
• So “recharging” of the nerve fiber is an active
metabolic process.
DEPT. OF PHYSIOLOGY, GMCM 24
Jens Skou
Nobel Prize in Physiology and Medicine 1997
DEPT. OF PHYSIOLOGY, GMCM 25
• Decrease in ECF calcium increase excitability
• By decreasing the amount of depolarization necessary
for opening of Na+ channels
• Increase in ECF calcium levels decreases excitability
and stabilizes the membrane
Effect of Ca2+ on excitability
DEPT. OF PHYSIOLOGY, GMCM 26
DEPT. OF PHYSIOLOGY, GMCM 27
Specific Learning Objectives
• Ionic Basis of Action Potential
• Properties of Action Potential
• Graded Potential v/s Action Potential
• Types of Action Potential
DEPT. OF PHYSIOLOGY, GMCM 29
PROPERTIES OF
ACTION POTENTIAL
30
Properties of Action Potential
1. Threshold stimulus
2. All or none response
3. Propagation of action potential
4. Refractory period
DEPT. OF PHYSIOLOGY, GMCM 31
• The stimulus that brings the membrane potential to the
firing level (–55 mV) is known as threshold stimulus.
• Threshold stimulus is defined as the lowest strength of
stimulus that elicits an action potential.
1. Threshold Stimulus
DEPT. OF PHYSIOLOGY, GMCM 32
Strength Duration Curve
DEPT. OF PHYSIOLOGY, GMCM 35
• Rheobase : minimum intensity of stimulus which
if applied for adequate time (utilization time)
produces a response.
• Chronaxie: minimum duration for which stimulus
of double the rheobase intensity must be applied to
produce a response
DEPT. OF PHYSIOLOGY, GMCM 36
• Within physiological limits, chronaxie of a given excitable tissue
is constant.
• Gives an idea about the excitability of a tissue. The lesser the
chronaxie, greater is the excitability.
• Nerves have a shorter chronaxie compared to muscles.
DEPT. OF PHYSIOLOGY, GMCM 37
Slowly rising currents fail to induce an action potential in
the nerve because the nerve undergoes adaptation.
DEPT. OF PHYSIOLOGY, GMCM 38
2. All or None Response
• Action potential fails to occur if the stimulus is
subthreshold in magnitude.
• It occurs with constant amplitude and shape
regardless of the strength of stimulus, if stimulus is at
or above threshold intensity.
DEPT. OF PHYSIOLOGY, GMCM 39
DEPT. OF PHYSIOLOGY, GMCM 40
2. All or None Response
• Action potential fails to occur if the stimulus is
subthreshold in magnitude
• It occurs with constant amplitude and shape
regardless of the strength of stimulus, if stimulus is
at or above threshold intensity
Why?
DEPT. OF PHYSIOLOGY, GMCM 41
• After the threshold level is achieved, the amount of sodium
influx becomes independent of the stimulus factor.
• The activation gates of voltage-gated Na+ channels open as
soon as -55mV is reached.
DEPT. OF PHYSIOLOGY, GMCM 42
3. Propagation of Action Potential (AP)
• AP elicited at any point on an excitable membrane
excites adjacent portions of the membrane.
• Results in propagation of AP along membrane.
DEPT. OF PHYSIOLOGY, GMCM 43
1. Excited portion rapidly develops ↑ permeability to
Na+ and influx begins
In unmyelinated axon
DEPT. OF PHYSIOLOGY, GMCM 44
DEPT. OF PHYSIOLOGY, GMCM 45
2. Positive charges from membrane ahead of and behind
AP flow into area of negativity - Current Sink
3. Charges are carried by inward-diffusing Na+ ions
through depolarized membrane for several millimeters
in both directions.
DEPT. OF PHYSIOLOGY, GMCM 46
DEPT. OF PHYSIOLOGY, GMCM 47
4. These positive charges increase the voltage to levels
above the threshold voltage for initiating an action
potential
5. So Na+ channels in these new areas immediately
open and the explosive action potential spreads
DEPT. OF PHYSIOLOGY, GMCM 48
DEPT. OF PHYSIOLOGY, GMCM 49
DEPT. OF PHYSIOLOGY, GMCM 50
Saltatory conduction (Myelinated Axon)
1. Myelin is an effective insulator, and current flow
through it is negligible
2. Depolarization travels from one node of Ranvier to
the next
DEPT. OF PHYSIOLOGY, GMCM 51
DEPT. OF PHYSIOLOGY, GMCM 52
3. Current sink at active node depolarize node ahead of
the action potential to firing level
4. This “jumping” of depolarization from node to node
is called saltatory conduction
5. So conduction up to 50 times faster than the fastest
unmyelinated fibers
DEPT. OF PHYSIOLOGY, GMCM 53
Advantages
1.The velocity of conduction is faster
2.Helps to conserves energy
In unmyelinated axons, voltage-gated channels open throughout
the axonal length causing activation of larger number of Na+-K+
ATPase and higher expenditure of energy.
DEPT. OF PHYSIOLOGY, GMCM 54
DEPT. OF PHYSIOLOGY, GMCM 55
1. Orthodromic conduction
2. Antidromic conduction
DEPT. OF PHYSIOLOGY, GMCM 56
• When AP is initiated in the middle of the axon, two
impulses traveling in opposite directions are set up.
• Impulses usually pass in one direction only, i.e., from
synaptic junctions or receptors along axons to their
termination – orthodromic conduction.
DEPT. OF PHYSIOLOGY, GMCM 57
• Since the impulse conducted in opposite
direction (antidromic) fails to pass the first
synapse they encounter & die out.
• Because synapses permit conduction only in
one direction.
DEPT. OF PHYSIOLOGY, GMCM 58
DEPT. OF PHYSIOLOGY, GMCM 59
NERVE PHYSIOLOGY- 5b
DR SARAN AJAY
DEPT. OF PHYSIOLOGY, GMCM
Specific Learning Objectives
• Ionic Basis of Action Potential
• Properties of Action Potential
• Properties of AP Continued
• Graded Potential v/s Action Potential
• Types of Action Potential
• Velocity of Nerve Conduction
• Properties of Mixed Nerve
DEPT. OF PHYSIOLOGY, GMCM 61
DEPT. OF PHYSIOLOGY, GMCM
Monophasic action potential
DEPT. OF PHYSIOLOGY, GMCM 63
Biphasic action potential
64
4. Refractory period
• Absolute Refractory Period
• Relative Refractory Period
DEPT. OF PHYSIOLOGY, GMCM 65
Absolute Refractory Period
• Period in which a stimulus, no matter how strong, will not
be able to excite the nerve
• Corresponds to the period from the firing level to the
point at which repolarization is about one-third
complete.
DEPT. OF PHYSIOLOGY, GMCM 66
DEPT. OF PHYSIOLOGY, GMCM 67
Basis
1. Shortly after action potential is initiated, Na+ channels
become inactivated.
2. No amount of excitatory signal will re-open inactivation
gates till membrane potential return to or near the RMP.
DEPT. OF PHYSIOLOGY, GMCM 68
DEPT. OF PHYSIOLOGY, GMCM 69
DEPT. OF PHYSIOLOGY, GMCM 70
Relative Refractory period
• Period in which a stimulus, stronger than normal
stimuli can cause excitation
• Corresponds to the period from the one-third of
repolarization to the start of after-depolarization
DEPT. OF PHYSIOLOGY, GMCM 71
Na+ channels reopen when membrane potential returns
to or near the original resting membrane potential.
DEPT. OF PHYSIOLOGY, GMCM 72
DEPT. OF PHYSIOLOGY, GMCM 74
Specific Learning Objectives
• Ionic Basis of Action Potential
• Properties of Action Potential
• Properties of AP Continued
• Graded Potential v/s Action Potential
• Types of Action Potential
• Velocity of Nerve Conduction
• Properties of Mixed Nerve
DEPT. OF PHYSIOLOGY, GMCM 76
DEPT. OF PHYSIOLOGY, GMCM
Graded Potential v/s Action Potential
DEPT. OF PHYSIOLOGY, GMCM 77
Graded potential Action potential
1. No threshold stimuli
needed
2. Amplitude of potential is
proportionate to the
intensity of stimulus
3. Can get summated
1. A threshold stimuli is
needed
2. Amplitude remains
constant even if intensity of
stimulus is increased above
threshold stimuli
3. Cannot be summated
DEPT. OF PHYSIOLOGY, GMCM 78
Graded potential Action potential
4. So does not obey “All or
none” law
5. Can be either depolarizing
or hyperpolarizing
6. Change in membrane
potential that is confined to
relatively small region on
membrane
4. Obeys “All or none” law
5. It is always depolarizing
6. Spreads over a larger area
on the membrane
DEPT. OF PHYSIOLOGY, GMCM 79
7. These potentials cannot be
conducted as impulses –
Non-propagating
potentials
8. No Refractory period
7. Can be conducted as
impulses – Propagating
potentials
8. Has a Refractory period
Graded potential Action potential
DEPT. OF PHYSIOLOGY, GMCM 80
Specific Learning Objectives
• Ionic Basis of Action Potential
• Properties of Action Potential
• Properties of AP Continued
• Graded Potential v/s Action Potential
• Types of Action Potential
• Velocity of Nerve Conduction
• Properties of Mixed Nerve
DEPT. OF PHYSIOLOGY, GMCM 82
DEPT. OF PHYSIOLOGY, GMCM
Types of Action Potentials
DEPT. OF PHYSIOLOGY, GMCM 83
Types of action potential
1. Spike potential (Nerve & Skeletal muscle)
2. Plateau potential (Cardiac muscle)
3. Rhythmic type of action potential
DEPT. OF PHYSIOLOGY, GMCM 84
Plateau potential
85
Rhythmic type of action potential
• Seen in rhythmically discharging cells
• SA node, AV node & conducting system of heart
• Smooth muscles of intestine & some neurons in CNS
• Pacemaker potential or pre-potential
DEPT. OF PHYSIOLOGY, GMCM 86
DEPT. OF PHYSIOLOGY, GMCM 87
DEPT. OF PHYSIOLOGY, GMCM 90
Specific Learning Objectives
• Ionic Basis of Action Potential
• Properties of Action Potential
• Properties of AP Continued
• Graded Potential v/s Action Potential
• Types of Action Potential
• Velocity of Nerve Conduction
• Properties of Mixed Nerve
DEPT. OF PHYSIOLOGY, GMCM
Velocity of Nerve Conduction
DEPT. OF PHYSIOLOGY, GMCM 91
Velocity of nerve conduction
Factors that increase velocity Factors that decrease velocity
Diameter Pressure
Myelination Narcotic drugs
Increase in Temperature Decrease in temperature
DEPT. OF PHYSIOLOGY, GMCM 92
“highly differentiated functions of single nerve fibers”
Erlanger and Gassser
Nobel Prize in Medicine
or Physiology, 1944
DEPT. OF PHYSIOLOGY, GMCM 93
Erlanger Gasser classification of nerve fibers
DEPT. OF PHYSIOLOGY, GMCM 94
DEPT. OF PHYSIOLOGY, GMCM 95
Numerical classification of sensory nerve fibers
DEPT. OF PHYSIOLOGY, GMCM 96
Susceptibility to Hypoxia, Pressure and LAs
DEPT. OF PHYSIOLOGY, GMCM 97
DEPT. OF PHYSIOLOGY, GMCM 99
Specific Learning Objectives
• Ionic Basis of Action Potential
• Properties of Action Potential
• Properties of AP Continued
• Graded Potential v/s Action Potential
• Types of Action Potential
• Velocity of Nerve Conduction
• Properties of Mixed Nerve
DEPT. OF PHYSIOLOGY, GMCM
Properties of a Mixed Nerve
DEPT. OF PHYSIOLOGY, GMCM 100
1. Effect of stimuli with different intensities
• Sub threshold stimulus
• Threshold stimulus
• Maximal stimulus
• Supra maximal stimulus
2. Compound action potential
DEPT. OF PHYSIOLOGY, GMCM 101
DEPT. OF PHYSIOLOGY, GMCM 102
• Potential changes recorded extracellularly from mixed nerves
represent an algebraic summation of the all-or-none action
potentials of many axons.
DEPT. OF PHYSIOLOGY, GMCM 103
• With subthreshold stimuli, no response occurs
• When the stimuli are of threshold intensity, axons
with low thresholds fire and a small potential change
is observed.
DEPT. OF PHYSIOLOGY, GMCM 104
1. Effect of stimuli with different intensities
• As the intensity of the stimulating current is increased,
the axons with higher thresholds are also stimulated
• Electrical response increases proportionately until
stimulus is strong enough to excite all of the axons
in the nerve
DEPT. OF PHYSIOLOGY, GMCM 105
• Stimulus that produces excitation of all the axons is the
maximal stimulus
• Application of greater, supramaximal stimuli produces
no further increase in the potential
DEPT. OF PHYSIOLOGY, GMCM 106
• In mixed nerves, there is the appearance of multiple
peaks in the action potential.
• The multipeaked action potential is called a
compound action potential.
DEPT. OF PHYSIOLOGY, GMCM 107
2. Compound action potential
DEPT. OF PHYSIOLOGY, GMCM 108
• Asynchronous discharge of the various fibers
• Different conduction velocities
DEPT. OF PHYSIOLOGY, GMCM 109
DEPT. OF PHYSIOLOGY, GMCM 110
WBC and Nerve Lecture Feedback (google.com)
DEPT. OF PHYSIOLOGY, GMCM 111
saran.adhoc@gmail.com
DEPT. OF PHYSIOLOGY, GMCM 113
DEPT. OF PHYSIOLOGY, GMCM 1
Q
Short Essay (8 marks)
1. Explain chronaxie, rheobase, utilization time. Draw strength
duration curve.
Write briefly (4 marks)
2. Ionic Basis of Resting membrane potential.
3. Ionic Basis of Action Potential.
4. Absolute Refractory Period.
Q - KUHS Mar 2021, May 2022
Q - KUHS Feb 2022, May 2022
Q - KUHS July 2022
Q - KUHS Feb 2016
Physiological Basis (2 marks)
1. Wallerian Degeneration
2. Sodium Potassium pump helps to maintain RMP.
Draw and Label
1. Action Potential in a Nerve
2. Multipolar Neuron
Q - KUHS July 2022
Q - KUHS Jan 2019
Q - KUHS Nov 2020, Sep 2021
Q - KUHS Aug 2015

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Nerve Physiology

  • 1. NERVE PHYSIOLOGY DR SARAN AJAY DEPT OF PHYSIOLOGY, GMCM
  • 2. DEPT OF PHYSIOLOGY, GMCM 10 What is an excitable tissue?
  • 3. Excitable Tissue • Property of responding to a stimulus is called excitability or irritability • A sudden and appreciable change in environment of living matter, lasting for a minimum time constitute a stimulus • Capable of generation of electrical impulses at their membranes
  • 4. • These impulses are used to transmit signals along the membranes • Mainly 2 excitable tissues – Nerve & muscle DEPT OF PHYSIOLOGY, GMCM 12
  • 5. • Nerves - specialized for function of reception, integration and transmission of information in the body • Muscles - also excitable tissues but are characterized by mechanical contraction DEPT OF PHYSIOLOGY, GMCM 13
  • 6. DEPT OF PHYSIOLOGY, GMCM 14 CNS : Central Nervous System PNS : Peripheral Nervous System NERVOUS SYSTEM
  • 7. Cellular elements of CNS • Neurons - basic building blocks • 1011 neurons • Also contain Glial cells • 40% of human genes participate in the formation of CNS
  • 9. DEPT OF PHYSIOLOGY, GMCM 19 STRUCTURE OF NEURON
  • 11. Cell body/ Soma/ Perikaryon 1. Round , stellate, pyramidal, fusiform 2. Nucleus with nucleoli 3. No centrosome 4. Cytoplasm – mitochondria, ER, Golgi apparatus, Nissl granules
  • 12. 5. Nissl granules • Basophilic granules • Contains rough ER • Involved in protein synthesis • Absent from axon & axon hillock • Chromatolysis - disintegrate and finally disappear DEPT OF PHYSIOLOGY, GMCM 22
  • 13. 7. Neurofibrils • Microfilaments and Microtubules • Alzheimer's disease: microfilament proteins → neurofibrillary tangles DEPT OF PHYSIOLOGY, GMCM 24
  • 16. 8. Pigment granules • Neuromelanin- in substantia nigra • Lipofuscin- aging neurons DEPT OF PHYSIOLOGY, GMCM 28
  • 17. Site of cell bodies • Gray matter of CNS • Autonomic and posterior nerve root ganglia Group of cell bodies • Inside the CNS- Nucleus • Outside CNS- Ganglia DEPT OF PHYSIOLOGY, GMCM 30
  • 18. Dendrites • Small multiple branched processes • Short course, irregular number • Contains Nissl bodies • Thorny projections – Dendritic spines • Impulses travel towards the cell body DEPT OF PHYSIOLOGY, GMCM 31
  • 19. Axon • Single long process • Arise from Axon hillock • Initial segment – first part of axon • Axolemma and axoplasm DEPT OF PHYSIOLOGY, GMCM 34
  • 21. • Axon divides into presynaptic terminals, which end in • Synaptic knobs/ terminal buttons/ axon telodendrion • Carries impulses away from cell body • Myelinated and unmyelinated nerve fibers DEPT OF PHYSIOLOGY, GMCM 36
  • 22. DEPT OF PHYSIOLOGY, GMCM 39 MYELINATION
  • 24. Myelination in PNS DEPT OF PHYSIOLOGY, GMCM 41
  • 25. • Schwann cell - wraps its membrane around an axon up to 100 times • Axons invaginate into cytoplasm of Schwann cell • So becomes suspended in a fold of Schwann cell membrane - mesaxon DEPT OF PHYSIOLOGY, GMCM 42
  • 27. • Lipids are deposited between the layers of Schwann cell • Compacted to form myelin sheath – by Protein zero( P0) • Extracellular portions of this membrane proteins on the apposing membranes lock to each other • Mutations in the gene for P0 → Peripheral neuropathy • Outermost cell membrane → Neurilemma DEPT OF PHYSIOLOGY, GMCM 46
  • 29. • Each Schwann cell provide myelin sheath for a short segment of axon • Between 2 segments - 1µm constrictions – Nodes of Ranvier • Myelin is absent at axonal endings DEPT OF PHYSIOLOGY, GMCM 48
  • 30. Functions of Myelin 1. Increases velocity of conduction: Saltatory conduction 2. Reduces energy expenditure for conduction 3. Acts as an insulator – prevents cross stimulation DEPT OF PHYSIOLOGY, GMCM 50
  • 32. In unmyelinated nerves, • Axon is surrounded by Schwann cell without wrapping of membrane DEPT OF PHYSIOLOGY, GMCM 52
  • 33. Myelination in CNS • Oligodendrocytes form myelin • They extend multiple processes and form myelin on many axons DEPT OF PHYSIOLOGY, GMCM 53
  • 35. Myelinogenesis • Begins at 4th month of intra uterine life • Sensory fibers – 4th-5th month • Pyramidal tract (motor fibers) – 2 years DEPT OF PHYSIOLOGY, GMCM 55
  • 36. 1. Babinski Test in children – Extensor Response 2. Mutations in gene for Protein0 → Peripheral neuropathies DEPT OF PHYSIOLOGY, GMCM 56 Applied Aspects
  • 37. 2. Multiple sclerosis - demyelinating disease • Autoimmune • Antibodies and WBCs attack myelin → inflammation & injury to the sheath → eventually the nerves are affected DEPT OF PHYSIOLOGY, GMCM 58
  • 38. • Loss of myelin → leakage of K+ through voltage-gated channels → hyperpolarization → failure to conduct impulses • Nerve conduction tests show slowed conduction in motor & sensory pathways • Numbness and weakness • Optic neuritis DEPT OF PHYSIOLOGY, GMCM 60
  • 39. NERVE PHYSIOLOGY- 2 DR SARAN AJAY DEPT OF PHYSIOLOGY, GMCM
  • 40. Specific Learning Objectives • Functional Zones of a Neuron • Classification of Neuron • Transport and Metabolism • Peripheral Nerve • Nerve Injury and Degeneration • Neuroglia • Neurotropins
  • 41. DEPT OF PHYSIOLOGY, GMCM 8 FUNCTIONAL ZONES OF A NEURON
  • 43. Functional Zones of a Neuron 1. Receptor zone- dendritic zone- local potentials 2. Site of origin of conducted impulses • Motor neuron – initial segment • Sensory – 1st node of Ranvier 3. Zone of all or none transmission- axon 4. Zone of secretion of neurotransmitters DEPT OF PHYSIOLOGY, GMCM 10
  • 44. Granules or vesicles – neurotransmitter Termination • Synapse • Effecter organ (muscle or gland) • Peripheral ganglion DEPT OF PHYSIOLOGY, GMCM 11
  • 46. Classification of neuron 1. Depending upon number of poles/ structural classification 2. Depending upon the function 3. Depending upon length of axon DEPT OF PHYSIOLOGY, GMCM 15
  • 47. A. Depending upon number of poles 1. Unipolar neuron • Single pole • Both dendrites and axon arise from that DEPT OF PHYSIOLOGY, GMCM 16
  • 48. DEPT OF PHYSIOLOGY, GMCM 17 2. Bipolar neuron 2 poles- one for axon, one for dendrite
  • 49. 3. Pseudo unipolar neuron • A subclass of bipolar cells • A single process splits into two, both of which function as axons • Peripheral one going to skin or muscle and central one to spinal cord • Eg: Dorsal root ganglion (DRG) DEPT OF PHYSIOLOGY, GMCM 18
  • 51. 4. Multi polar neuron • One pole- axon • Other poles- dendrites DEPT OF PHYSIOLOGY, GMCM 20 Q. KUHS AUGUST 2015
  • 53. B. Depending on function 1. Sensory /afferent neuron 2. Motor / efferent neuron 3. Interneuron DEPT OF PHYSIOLOGY, GMCM 22
  • 54.
  • 55. C. Depending upon length of axon Golgi type 1- also known as projection neurons • Have long axons • Neurons forming peripheral nerves & long tracts of brain Golgi type 2- short circuit neuron • Short axons • Numerous in cerebral cortex, cerebellar cortex, retina DEPT OF PHYSIOLOGY, GMCM 24
  • 56. Biological activities in a neuron • Protein synthesis & transport • Metabolism • Excitation and conduction of impulses
  • 57. Protein synthesis & Transport • Soma is the machinery for protein synthesis • Neurotransmitters and other proteins that are needed at the axon terminals • Transport of proteins and polypeptides to axonal ending occurs by axoplasmic flow
  • 58.
  • 59. Axoplasmic flow/ transport 1. Anterograde transport: from cell body → axon terminal • Fast axonal transport- 400 mm/day • Slow axonal transport- 0.5-10 mm/day
  • 60. • Occurs along microtubules • Requires 2 molecular motors Dynein & Kinesin
  • 61.
  • 62.
  • 63. Substances transported are • Fast Axonal transport 1. Mitochondria and other membrane bound organelles 2. Small Vesicles 3. Actin and Myosin • Slow Axonal Transport 1. Tubulins of microtubules 2. Protein subunits of neurofilaments
  • 64. 2. Retrograde transport • From axon terminal → cell body • 200mm/ day • Occurs along microtubules
  • 65. Substances transported are 1. Used synaptic vesicles, 2. Nerve growth factors (NGF) 3. Viruses like polio, herpes simplex and rabies 4. Toxins e.g.: tetanus toxin
  • 66.
  • 67.
  • 68. Metabolism • Low level • 70% total energy is used to maintain the polarity of membrane • By action of Na+- K+ ATPase • At maximum activity– metabolic rate doubles
  • 69.
  • 70. Peripheral Nerve • Compact bundle of axons located outside CNS – Nerve • Axons are arranged in different bundles – Fasciculi • Each axon is covered by Endoneurium • Each fasciculus is covered by Perineurium • Whole nerve is covered by Epineurium
  • 71.
  • 73. Response to injury Types of injury • Cut injury • Crush injury • Ischemia • Injection of toxic substance • Diseases like DM, syphilis • Pressure on the nerve
  • 74. A. Physical and chemical degenerative changes 1. Axon distal to the injury (anterograde degeneration) 2. Proximal to the injury 3. Cell body (retrograde degeneration)
  • 75.
  • 76. 1. Anterograde degeneration (Wallerian) • Axon distal to the injury • Augustus Waller Q. KUHS 2022 JULY
  • 77. a) Changes in impulse conduction b) Changes in the axon c) Changes in the myelin sheath d) Changes in the Neurilemma – Ghost tube
  • 78. a. Changes in impulse conduction 1. If severed - stops within hours 2. If crushed • Up to 3 days normal conduction • After 3 days deteriorates seriously • After 5 days no impulse evoked
  • 79. b. Changes in Axon 1. Swells up 2. Irregular in shape 3. Breaks into small fragments 4. Axon terminals retract from post synaptic target 5. Within several weeks axon and its terminals degenerate
  • 80.
  • 81. c. Myelin Sheath 1. Small fragments 2. Hydrolysis of myelin to fatty droplets 3. Begins by 8th day and completed by 32 days
  • 82. d. Neurilemma 1. Intact 2. Schwann cells – increase size and multiply 3. Macrophages remove degenerating axons, myelin and cellular debris 4. Neurilemmal tube becomes empty – Ghost tube
  • 83. 2. Retrograde degeneration • Proximal to injury • Similar to changes seen in distal part of axon • Occurs only up to first or second node of Ranvier • Changes seen in proximal part of axon along with those in cell body constitute retrograde degeneration
  • 84. 3. Changes in cell body • Starts within 48hr → continues up to 15-20 days • Cell organelles are fragmented and eventually disappear • Cell body draws in more fluid, swells up • Nissl substances undergo Chromatolysis • Nucleus is displaced to periphery and extruded out of cell
  • 85. B. Regeneration Under favorable conditions • Neurilemma present • Cell body & nucleus are intact • Gap less than 3mm • Sliced cut, cut ends in straight line
  • 86. • Starts within 4 days of injury • More active after 30 days • Complete recovery- several months to one year • 1 – 4 mm per day
  • 87. Changes in the axon • From proximal stump axon elongates and give out fibrils • Schwann cells of distal end guide the fibril to enter the endo neural tube • Fibril makes contact with the peripheral end organ • Myelination – completed in 1 year • 80% of original diameter is regained
  • 88.
  • 89. Changes in the cell body • 20-80d • Nissl granules followed by Golgi apparatus appear in cell body • Cell loses excess water, regains its normal size • Nucleus occupies the central position
  • 90.
  • 91.
  • 92.
  • 93. Complication following nerve injury 1. Complete atrophy 2. Functional complications- misinterpretation of sensations 3. Neuroma formation- if fibrils could not find distal cut end, it will form a mass
  • 94. 4. Phantom Limb • Feeling perceived by a patient after amputation of limb • Neuroma when stimulated, patient feel the lost limb
  • 96. NERVE PHYSIOLOGY- 2b DR SARAN AJAY DEPT OF PHYSIOLOGY, GMCM
  • 97. Specific Learning Objectives • Functional Zones of a Neuron • Classification of Neuron • Transport and Metabolism • Peripheral Nerve • Nerve Injury and Degeneration • Neuroglia • Neurotropins
  • 98. Glial cells/ Neuroglia • Supporting cells in nervous system • 2 types: Microglia & Macroglia • Microglia arise from macrophages • Act as scavenger cells – remove debris resulting from injury, infection, and diseases
  • 99. • Macroglia: Oligodendrocytes, Schwann cells, & Astrocytes • Oligodendrocytes • In white matter provide myelin • In gray matter support neurons • Schwann cells provide myelin to PNS • Astrocytes most common glia in the CNS, star like shape
  • 100.
  • 101.
  • 102. Astrocytes Astrocytes help to regulate the microenvironment in CNS under normal conditions and also in response to damage.
  • 103. • Fibrous • contain intermediate filaments • found in white matter • Protoplasmic – found in gray matter
  • 104. Functions • Astrocytes send processes to blood vessels → induce capillaries to form tight junctions → Blood–brain barrier • Also send processes that envelop synapses and surface of nerve cells • Produce neurotropins
  • 105.
  • 106. • Help to maintain concentration of ions and neurotransmitters • Regulate microenvironment of neuron • Membrane potential of protoplasmic astrocyte varies with external K+
  • 107.
  • 108. Specific Learning Objectives • Functional Zones of a Neuron • Classification of Neuron • Transport and Metabolism • Peripheral Nerve • Nerve Injury and Degeneration • Neuroglia • Neurotropins
  • 109. Neurotrophins • Proteins necessary for survival and growth of neurons • Site of production- muscles, structures innervated by neuron, astrocytes, neurons • Retrograde transport and Anterograde transport
  • 110. Nerve growth factor (NGF) • First neurotrophin identified • Sympathetic nerves, sensory nerves • Trk A Receptor Brain derived neurotrophic factor (BDNF) • Trk B • Peripheral sensory nerves
  • 111. Neurotrophin -3 • Trk B and Trk C • Cutaneous mechanoreceptors • Proprioceptor neurons that innervate muscle spindle
  • 112. Specific Learning Objectives • Functional Zones of a Neuron • Classification of Neuron • Transport and Metabolism • Peripheral Nerve • Nerve Injury and Degeneration • Neuroglia • Neurotropins
  • 113. NERVE PHYSIOLOGY- 3 DR SARAN AJAY DEPT. OF PHYSIOLOGY, GMCM
  • 114. Hodgkin and Huxley Nobel Prize in Physiology and Medicine 1963
  • 115. Specific Learning Objectives • Membrane Potential • Resting Membrane Potential • Genesis of RMP • Electrotonic Potentials DEPT. OF PHYSIOLOGY, GMCM 7
  • 117. • The potential difference across the membrane of all living cells • Results from the separation of charges across the cell membrane DEPT. OF PHYSIOLOGY, GMCM 9
  • 121. • Note that the membrane itself is not charged. • The term membrane potential refers to the difference in charge between the wafer-thin regions of ICF and ECF lying next to the inside and outside of the membrane, respectively. DEPT. OF PHYSIOLOGY, GMCM 13
  • 123. 1. Transport processes 2. Signaling purposes DEPT. OF PHYSIOLOGY, GMCM 16
  • 124. • The energy stored in this miniature battery can drive a variety of transmembrane transport processes. • Electrically excitable cells such as brain neurons and heart myocytes also use this energy for signalling purposes. The brief electrical impulses produced by such cells are called action potentials. DEPT. OF PHYSIOLOGY, GMCM 17
  • 125. More the separation of charges, more is the membrane potential. DEPT. OF PHYSIOLOGY, GMCM 18
  • 126. • The inside is negative with respect to the outside • Varies from cell to cell • Varies with functional status DEPT. OF PHYSIOLOGY, GMCM 19
  • 127. • The cells of excitable tissues—namely, nerve cells and muscle cells—have the ability to produce rapid, transient changes in their membrane potential when excited. • These brief fluctuations in potential serve as electrical signals or action potentials. DEPT. OF PHYSIOLOGY, GMCM 20
  • 128. Specific Learning Objectives • Membrane Potential • Resting Membrane Potential • Genesis of RMP • Electrotonic Potentials DEPT. OF PHYSIOLOGY, GMCM 22
  • 129. • It is the potential difference across the membrane while the cell is at rest. Neuron : - 70mV Skeletal & cardiac muscle : - 90mV RBC : - 10mV • Transmembrane / Steady state potential / Diffusion potential Resting Membrane Potential DEPT. OF PHYSIOLOGY, GMCM 23
  • 130. • The constant membrane potential present in the cells of non excitable tissues and those of excitable tissues when they are at rest—that is, when they are not producing electrical signals—is known as the resting membrane potential. DEPT. OF PHYSIOLOGY, GMCM 24
  • 131. Recording of RMP DEPT. OF PHYSIOLOGY, GMCM 25
  • 132. • Microelectrodes • Amplifier • Voltmeter • Cathode Ray Oscilloscope (CRO) for rapid changes Equipment DEPT. OF PHYSIOLOGY, GMCM 26
  • 133. Specific Learning Objectives • Membrane Potential • Resting Membrane Potential • Genesis of RMP • Electrotonic Potentials DEPT. OF PHYSIOLOGY, GMCM 28
  • 134. Genesis of RMP • Due to the unequal distribution of ions across the cell membrane (concentration gradient) • Their selective movement through the cell membrane DEPT. OF PHYSIOLOGY, GMCM 29
  • 135. The ions primarily responsible for RMP 1. Na+ 2. K+ 3. A- A- = Large, negatively charged (anionic) intracellular proteins DEPT. OF PHYSIOLOGY, GMCM 30
  • 136. FACTORS involved in Genesis of RMP 5 DEPT. OF PHYSIOLOGY, GMCM 31
  • 137. “The phenomenon of predictable and unequal distribution of permeant charged ions on either side of a semipermeable membrane, in the presence of impermeant charged ions” 1. The Gibbs-Donnan effect DEPT. OF PHYSIOLOGY, GMCM 33
  • 139. DEPT. OF PHYSIOLOGY, GMCM 36 Non permeable anion
  • 143. “The phenomenon of predictable and unequal distribution of permeant charged ions on either side of a semipermeable membrane, in the presence of impermeant charged ions” The Gibbs-Donnan effect DEPT. OF PHYSIOLOGY, GMCM 41
  • 144. When 2 ionized solutions are separated by a semi- permeable membrane, at equilibrium 1. Each solution will be electrically neutral 2. (Diffusible cations)A X (Diffusible anions)A = (Diffusible cations)B X (Diffusible anions)B DEPT. OF PHYSIOLOGY, GMCM 43
  • 145. • Diffusible cations (K+) more on the side of non-diffusible anions (proteins) : ICF • Less diffusible cations (Na+) more on the side of diffusible anions (Cl-) : ECF DEPT. OF PHYSIOLOGY, GMCM 44
  • 146. Na+, Cl- K+ K+ , anions Na+ ,Cl- ECF ICF DEPT. OF PHYSIOLOGY, GMCM 45
  • 147. Ions ECF mmol/L ICF mmol/L Na+ 150 15 K+ 5.5 150 Cl- 125 9 Proteins 0 65 Distribution of ions DEPT. OF PHYSIOLOGY, GMCM 46
  • 148. 2. Selective Permeability of the cell membrane • Separates ECF & ICF DEPT. OF PHYSIOLOGY, GMCM 47
  • 149. • Cytoplasm has diffusible & non-diffusible ions • Membrane is freely permeable to K+ and Cl- • Moderately permeable to Na+ • Impermeable to intracellular proteins and organic phosphates (negatively charged ions) DEPT. OF PHYSIOLOGY, GMCM 48
  • 150. Permeability to K+ • Potassium sodium leak channels • About 50-100 times than that for Na+ • Hydrated K+ ion is smaller DEPT. OF PHYSIOLOGY, GMCM 49
  • 151. • K+ efflux - not compensated by Na influx • K+ efflux is not accompanied by negatively charged anions • More negative ions remain inside the cell → creates negativity inside the cell DEPT. OF PHYSIOLOGY, GMCM 50
  • 152. Asymmetric distribution of ions ↓ Concentration & Electrical gradients ↓ Diffusion DEPT. OF PHYSIOLOGY, GMCM 52
  • 153. K+ as the only diffusible ion DEPT. OF PHYSIOLOGY, GMCM 54
  • 155. ECF 5.5 mmol/L of H2O ICF 150 mmol/L of H2O C G E G DEPT. OF PHYSIOLOGY, GMCM 56
  • 156. • Equilibrium is reached • Driving forces down conc. & electrical gradients are equal and opposite • No net movement DEPT. OF PHYSIOLOGY, GMCM 57
  • 157. 3. Nernst Equation DEPT. OF PHYSIOLOGY, GMCM 59
  • 158. Nernst potential/ Equilibrium potential for K+ Ek = -61.5 log [Ki + ] = - 90mV (37 degC) [Ko +] [Ko +] = K+ concentration outside the cell [Ki +] = K+ concentration inside the cell DEPT. OF PHYSIOLOGY, GMCM 60
  • 160. K+ as the only diffusible ion DEPT. OF PHYSIOLOGY, GMCM 62
  • 162. 1. Polarity/ electrical charge 2. Permeability of membrane to each 3. Concentration inside & outside When multiple ions are involved, Membrane potential depends on DEPT. OF PHYSIOLOGY, GMCM 64
  • 163. 4. Goldman Hodgkin – Katz equation • With this equation RMP calculated is –67 mV DEPT. OF PHYSIOLOGY, GMCM 65
  • 165. • Greater the permeability of an ion, greater is the tendency for that ion to drive the membrane potential towards its own equilibrium potential DEPT. OF PHYSIOLOGY, GMCM 67
  • 166. 5. Na+ - K+ ATPase • Steady ion leaks cannot continue forever without eventually dissipating the ion gradients • This is prevented by the Na+-K+ ATPase • It actively moves 3 Na+ out and 2 K+ in against their electrochemical gradients DEPT. OF PHYSIOLOGY, GMCM 69
  • 167. Jens Skou Nobel Prize in Physiology and Medicine 1997
  • 169. • Results in continuous loss of positive charges from inside the membrane • Creates an additional degree of negativity • So it is electrogenic and contributes to RMP about – 4mV • Helps to maintain osmotic balance. DEPT. OF PHYSIOLOGY, GMCM 72
  • 170. 1. Donnan effect & Gibbs Donnan Equilibrium 2. Selective permeability of cell membrane to ions 3. Nernst Equation 4. Goldman Hodgkin Katz Equation 5. Sodium- potassium ATPase pump Factors involved in genesis of RMP DEPT. OF PHYSIOLOGY, GMCM 73
  • 171. Factors affecting RMP 1. ECF K+ concentration ECF K+ ↑: magnitude of RMP ↓ → neuron becomes more excitable 2. Inhibition of Na+ K+ ATPase 3. ECF Na+: no effect DEPT. OF PHYSIOLOGY, GMCM 74
  • 172. • If the extracellular level of K + is increased (hyperkalemia), the resting potential moves closer to the threshold for eliciting an action potential, thus the neuron becomes more excitable. • If the extracellular level of K + is decreased (hypokalemia), the membrane potential is reduced and the neuron is hyperpolarized. DEPT. OF PHYSIOLOGY, GMCM 75
  • 173. NERVE PHYSIOLOGY- 4 DR SARAN AJAY DEPT. OF PHYSIOLOGY, GMCM
  • 174. Electrical Properties of a Neuron 1. Excitability 2. Conductivity DEPT. OF PHYSIOLOGY, GMCM 3
  • 175. Excitability • Stimulus • Types • Strength/ intensity Threshold stimulus Subthreshold stimulus Suprathreshold stimulus DEPT. OF PHYSIOLOGY, GMCM 4
  • 176. Application of stimulus will produce 1. Local non-propagated potentials Electrotonic potentials 2. Propagated potentials Action potential/ nerve impulse DEPT. OF PHYSIOLOGY, GMCM 5
  • 177. Specific Learning Objectives • Electrotonic Potential • Action Potential • Ionic Basis of Action Potential • Graded Potential v/s Action Potential
  • 179. • Demonstrated by placing recording electrodes within a few millimeters of a stimulating electrode • Applying subthreshold stimuli of fixed duration DEPT. OF PHYSIOLOGY, GMCM 12 Recording of electrotonic potential
  • 181. • Leads to a localized potential change • Rises sharply and decays exponentially with time • Graded response can be produced both at cathode and anode 1. Catelectrotonic potential 2. Anelectrotonic potential DEPT. OF PHYSIOLOGY, GMCM 14
  • 184. Graded Potential – Examples 1. End plate potential 2. Post synaptic potential 3. Generator or receptor potential DEPT. OF PHYSIOLOGY, GMCM 18
  • 185. Specific Learning Objectives • Electrotonic Potential • Action Potential • Ionic Basis of Action Potential • Graded Potential v/s Action Potential
  • 187. • Brief, rapid, large depolarizing changes in membrane potential • Transiently, resting negative potential → positive potential • Conducted, propagated along the nerve fiber • Non decremental fashion • Nerve signals are transmitted by action potentials
  • 188. How is an action potential recorded? 1. Stimulating Electrodes (min - threshold stimuli) 2. Recording Electrodes 3. Amplifier 4. Cathode Ray Oscilloscope
  • 190. 1. Resting stage 2. Depolarization 3. Repolarization Stages of Action Potential
  • 191.
  • 192. 1. RMP –70mV (polarized state) 2. Stimulus artifact 3. Latent period (Isoelectric potential interval) 4. Depolarization (reverse polarization) 5. Firing level 6. Spike potential 7. After depolarization 8. After hyperpolarization
  • 193. Marked changes in membrane permeability and ion movement lead to action potential.
  • 194. NERVE PHYSIOLOGY- 5 DR SARAN AJAY DEPT. OF PHYSIOLOGY, GMCM
  • 195. Specific Learning Objectives • Ionic Basis of Action Potential • Properties of Action Potential • Graded Potential v/s Action Potential • Types of Action Potential DEPT. OF PHYSIOLOGY, GMCM 4
  • 196. IONIC BASIS OF ACTION POTENTIAL DEPT. OF PHYSIOLOGY, GMCM 5
  • 197. 1. Stimulus artifact – Current leakage from stimulating to recording electrodes 2. Latent Period – Time taken by the impulse to travel along the axon • Distance between electrodes • Velocity of conduction DEPT. OF PHYSIOLOGY, GMCM 6
  • 198. 3. Depolarization Threshold stimulus ↓ Initial slow depolarization (a change of 7–15mV) (opening of few voltage gated Na+ channels) DEPT. OF PHYSIOLOGY, GMCM 7
  • 199. Voltage Gated Sodium Channel DEPT. OF PHYSIOLOGY, GMCM 8
  • 200. Threshold stimulus ↓ Initial slow depolarization (a change of 7–15mV) (opening of few voltage gated Na+ channels) ↓ Rapid depolarization (at –55mV) Firing Level (opening of more and more voltage gated Na+ channels) DEPT. OF PHYSIOLOGY, GMCM 9
  • 201. Feedback Control in Voltage Gated Ion Channels / Hodgkin Cycle DEPT. OF PHYSIOLOGY, GMCM 10
  • 202. Firing Level • At -55mV more Na channels opens → gush of Na+ into cell (500 – 5000 fold) DEPT. OF PHYSIOLOGY, GMCM 11
  • 203. • Membrane potential moves towards equilibrium potential for Na+ : +61 mV • But membrane potential does not reach to +61 mV because Na+ conductance is short lived. DEPT. OF PHYSIOLOGY, GMCM 12
  • 206. 1. After few 10,000th of a second inactivation gate closed → Na+ influx ↓ • Inactivation gate will remain closed till (or near) reaching RMP again. 4. Repolarization DEPT. OF PHYSIOLOGY, GMCM 15
  • 207. 2. Direction of electrical gradient of Na+ is reversed during overshoot • Leads to decrease in Na+ influx 3. Opening of voltage gated K+ channel also contributes to repolarization DEPT. OF PHYSIOLOGY, GMCM 16
  • 208. Voltage Gated Potassium Channel DEPT. OF PHYSIOLOGY, GMCM 17
  • 209. • Only 1 gate inside, resting state gate is closed • As membrane potential rises -70 to 0 → slow conformational change in the K+ gate occurs → opening of gate • So repolarization is due to both ↑ K+ efflux and ↓ Na+ influx DEPT. OF PHYSIOLOGY, GMCM 18
  • 210. Feedback Control in Voltage Gated Ion Channels DEPT. OF PHYSIOLOGY, GMCM 19
  • 213. 5. After depolarization due to slowing of K+ efflux 6. After hyperpolarization due to slow return of K+ channel to closed state DEPT. OF PHYSIOLOGY, GMCM 22
  • 214. 7. Re-establishing Na+ and K+ ionic gradients • Transmission of action potential slightly reduces concentration differences of Na+ and K+ inside and outside the membrane DEPT. OF PHYSIOLOGY, GMCM 23
  • 215. • Achieved by action of the Na+ - K+ pump • This pump requires energy derived from ATP • So “recharging” of the nerve fiber is an active metabolic process. DEPT. OF PHYSIOLOGY, GMCM 24
  • 216. Jens Skou Nobel Prize in Physiology and Medicine 1997 DEPT. OF PHYSIOLOGY, GMCM 25
  • 217. • Decrease in ECF calcium increase excitability • By decreasing the amount of depolarization necessary for opening of Na+ channels • Increase in ECF calcium levels decreases excitability and stabilizes the membrane Effect of Ca2+ on excitability DEPT. OF PHYSIOLOGY, GMCM 26
  • 219. Specific Learning Objectives • Ionic Basis of Action Potential • Properties of Action Potential • Graded Potential v/s Action Potential • Types of Action Potential DEPT. OF PHYSIOLOGY, GMCM 29
  • 221. Properties of Action Potential 1. Threshold stimulus 2. All or none response 3. Propagation of action potential 4. Refractory period DEPT. OF PHYSIOLOGY, GMCM 31
  • 222. • The stimulus that brings the membrane potential to the firing level (–55 mV) is known as threshold stimulus. • Threshold stimulus is defined as the lowest strength of stimulus that elicits an action potential. 1. Threshold Stimulus DEPT. OF PHYSIOLOGY, GMCM 32
  • 223. Strength Duration Curve DEPT. OF PHYSIOLOGY, GMCM 35
  • 224. • Rheobase : minimum intensity of stimulus which if applied for adequate time (utilization time) produces a response. • Chronaxie: minimum duration for which stimulus of double the rheobase intensity must be applied to produce a response DEPT. OF PHYSIOLOGY, GMCM 36
  • 225. • Within physiological limits, chronaxie of a given excitable tissue is constant. • Gives an idea about the excitability of a tissue. The lesser the chronaxie, greater is the excitability. • Nerves have a shorter chronaxie compared to muscles. DEPT. OF PHYSIOLOGY, GMCM 37
  • 226. Slowly rising currents fail to induce an action potential in the nerve because the nerve undergoes adaptation. DEPT. OF PHYSIOLOGY, GMCM 38
  • 227. 2. All or None Response • Action potential fails to occur if the stimulus is subthreshold in magnitude. • It occurs with constant amplitude and shape regardless of the strength of stimulus, if stimulus is at or above threshold intensity. DEPT. OF PHYSIOLOGY, GMCM 39
  • 229. 2. All or None Response • Action potential fails to occur if the stimulus is subthreshold in magnitude • It occurs with constant amplitude and shape regardless of the strength of stimulus, if stimulus is at or above threshold intensity Why? DEPT. OF PHYSIOLOGY, GMCM 41
  • 230. • After the threshold level is achieved, the amount of sodium influx becomes independent of the stimulus factor. • The activation gates of voltage-gated Na+ channels open as soon as -55mV is reached. DEPT. OF PHYSIOLOGY, GMCM 42
  • 231. 3. Propagation of Action Potential (AP) • AP elicited at any point on an excitable membrane excites adjacent portions of the membrane. • Results in propagation of AP along membrane. DEPT. OF PHYSIOLOGY, GMCM 43
  • 232. 1. Excited portion rapidly develops ↑ permeability to Na+ and influx begins In unmyelinated axon DEPT. OF PHYSIOLOGY, GMCM 44
  • 234. 2. Positive charges from membrane ahead of and behind AP flow into area of negativity - Current Sink 3. Charges are carried by inward-diffusing Na+ ions through depolarized membrane for several millimeters in both directions. DEPT. OF PHYSIOLOGY, GMCM 46
  • 236. 4. These positive charges increase the voltage to levels above the threshold voltage for initiating an action potential 5. So Na+ channels in these new areas immediately open and the explosive action potential spreads DEPT. OF PHYSIOLOGY, GMCM 48
  • 239. Saltatory conduction (Myelinated Axon) 1. Myelin is an effective insulator, and current flow through it is negligible 2. Depolarization travels from one node of Ranvier to the next DEPT. OF PHYSIOLOGY, GMCM 51
  • 241. 3. Current sink at active node depolarize node ahead of the action potential to firing level 4. This “jumping” of depolarization from node to node is called saltatory conduction 5. So conduction up to 50 times faster than the fastest unmyelinated fibers DEPT. OF PHYSIOLOGY, GMCM 53
  • 242. Advantages 1.The velocity of conduction is faster 2.Helps to conserves energy In unmyelinated axons, voltage-gated channels open throughout the axonal length causing activation of larger number of Na+-K+ ATPase and higher expenditure of energy. DEPT. OF PHYSIOLOGY, GMCM 54
  • 244. 1. Orthodromic conduction 2. Antidromic conduction DEPT. OF PHYSIOLOGY, GMCM 56
  • 245. • When AP is initiated in the middle of the axon, two impulses traveling in opposite directions are set up. • Impulses usually pass in one direction only, i.e., from synaptic junctions or receptors along axons to their termination – orthodromic conduction. DEPT. OF PHYSIOLOGY, GMCM 57
  • 246. • Since the impulse conducted in opposite direction (antidromic) fails to pass the first synapse they encounter & die out. • Because synapses permit conduction only in one direction. DEPT. OF PHYSIOLOGY, GMCM 58
  • 248. NERVE PHYSIOLOGY- 5b DR SARAN AJAY DEPT. OF PHYSIOLOGY, GMCM
  • 249. Specific Learning Objectives • Ionic Basis of Action Potential • Properties of Action Potential • Properties of AP Continued • Graded Potential v/s Action Potential • Types of Action Potential • Velocity of Nerve Conduction • Properties of Mixed Nerve DEPT. OF PHYSIOLOGY, GMCM 61 DEPT. OF PHYSIOLOGY, GMCM
  • 250. Monophasic action potential DEPT. OF PHYSIOLOGY, GMCM 63
  • 252. 4. Refractory period • Absolute Refractory Period • Relative Refractory Period DEPT. OF PHYSIOLOGY, GMCM 65
  • 253. Absolute Refractory Period • Period in which a stimulus, no matter how strong, will not be able to excite the nerve • Corresponds to the period from the firing level to the point at which repolarization is about one-third complete. DEPT. OF PHYSIOLOGY, GMCM 66
  • 255. Basis 1. Shortly after action potential is initiated, Na+ channels become inactivated. 2. No amount of excitatory signal will re-open inactivation gates till membrane potential return to or near the RMP. DEPT. OF PHYSIOLOGY, GMCM 68
  • 258. Relative Refractory period • Period in which a stimulus, stronger than normal stimuli can cause excitation • Corresponds to the period from the one-third of repolarization to the start of after-depolarization DEPT. OF PHYSIOLOGY, GMCM 71
  • 259. Na+ channels reopen when membrane potential returns to or near the original resting membrane potential. DEPT. OF PHYSIOLOGY, GMCM 72
  • 261. Specific Learning Objectives • Ionic Basis of Action Potential • Properties of Action Potential • Properties of AP Continued • Graded Potential v/s Action Potential • Types of Action Potential • Velocity of Nerve Conduction • Properties of Mixed Nerve DEPT. OF PHYSIOLOGY, GMCM 76 DEPT. OF PHYSIOLOGY, GMCM
  • 262. Graded Potential v/s Action Potential DEPT. OF PHYSIOLOGY, GMCM 77
  • 263. Graded potential Action potential 1. No threshold stimuli needed 2. Amplitude of potential is proportionate to the intensity of stimulus 3. Can get summated 1. A threshold stimuli is needed 2. Amplitude remains constant even if intensity of stimulus is increased above threshold stimuli 3. Cannot be summated DEPT. OF PHYSIOLOGY, GMCM 78
  • 264. Graded potential Action potential 4. So does not obey “All or none” law 5. Can be either depolarizing or hyperpolarizing 6. Change in membrane potential that is confined to relatively small region on membrane 4. Obeys “All or none” law 5. It is always depolarizing 6. Spreads over a larger area on the membrane DEPT. OF PHYSIOLOGY, GMCM 79
  • 265. 7. These potentials cannot be conducted as impulses – Non-propagating potentials 8. No Refractory period 7. Can be conducted as impulses – Propagating potentials 8. Has a Refractory period Graded potential Action potential DEPT. OF PHYSIOLOGY, GMCM 80
  • 266. Specific Learning Objectives • Ionic Basis of Action Potential • Properties of Action Potential • Properties of AP Continued • Graded Potential v/s Action Potential • Types of Action Potential • Velocity of Nerve Conduction • Properties of Mixed Nerve DEPT. OF PHYSIOLOGY, GMCM 82 DEPT. OF PHYSIOLOGY, GMCM
  • 267. Types of Action Potentials DEPT. OF PHYSIOLOGY, GMCM 83
  • 268. Types of action potential 1. Spike potential (Nerve & Skeletal muscle) 2. Plateau potential (Cardiac muscle) 3. Rhythmic type of action potential DEPT. OF PHYSIOLOGY, GMCM 84
  • 270. Rhythmic type of action potential • Seen in rhythmically discharging cells • SA node, AV node & conducting system of heart • Smooth muscles of intestine & some neurons in CNS • Pacemaker potential or pre-potential DEPT. OF PHYSIOLOGY, GMCM 86
  • 272. DEPT. OF PHYSIOLOGY, GMCM 90 Specific Learning Objectives • Ionic Basis of Action Potential • Properties of Action Potential • Properties of AP Continued • Graded Potential v/s Action Potential • Types of Action Potential • Velocity of Nerve Conduction • Properties of Mixed Nerve DEPT. OF PHYSIOLOGY, GMCM
  • 273. Velocity of Nerve Conduction DEPT. OF PHYSIOLOGY, GMCM 91
  • 274. Velocity of nerve conduction Factors that increase velocity Factors that decrease velocity Diameter Pressure Myelination Narcotic drugs Increase in Temperature Decrease in temperature DEPT. OF PHYSIOLOGY, GMCM 92
  • 275. “highly differentiated functions of single nerve fibers” Erlanger and Gassser Nobel Prize in Medicine or Physiology, 1944 DEPT. OF PHYSIOLOGY, GMCM 93
  • 276. Erlanger Gasser classification of nerve fibers DEPT. OF PHYSIOLOGY, GMCM 94
  • 278. Numerical classification of sensory nerve fibers DEPT. OF PHYSIOLOGY, GMCM 96
  • 279. Susceptibility to Hypoxia, Pressure and LAs DEPT. OF PHYSIOLOGY, GMCM 97
  • 280. DEPT. OF PHYSIOLOGY, GMCM 99 Specific Learning Objectives • Ionic Basis of Action Potential • Properties of Action Potential • Properties of AP Continued • Graded Potential v/s Action Potential • Types of Action Potential • Velocity of Nerve Conduction • Properties of Mixed Nerve DEPT. OF PHYSIOLOGY, GMCM
  • 281. Properties of a Mixed Nerve DEPT. OF PHYSIOLOGY, GMCM 100
  • 282. 1. Effect of stimuli with different intensities • Sub threshold stimulus • Threshold stimulus • Maximal stimulus • Supra maximal stimulus 2. Compound action potential DEPT. OF PHYSIOLOGY, GMCM 101
  • 283. DEPT. OF PHYSIOLOGY, GMCM 102
  • 284. • Potential changes recorded extracellularly from mixed nerves represent an algebraic summation of the all-or-none action potentials of many axons. DEPT. OF PHYSIOLOGY, GMCM 103
  • 285. • With subthreshold stimuli, no response occurs • When the stimuli are of threshold intensity, axons with low thresholds fire and a small potential change is observed. DEPT. OF PHYSIOLOGY, GMCM 104 1. Effect of stimuli with different intensities
  • 286. • As the intensity of the stimulating current is increased, the axons with higher thresholds are also stimulated • Electrical response increases proportionately until stimulus is strong enough to excite all of the axons in the nerve DEPT. OF PHYSIOLOGY, GMCM 105
  • 287. • Stimulus that produces excitation of all the axons is the maximal stimulus • Application of greater, supramaximal stimuli produces no further increase in the potential DEPT. OF PHYSIOLOGY, GMCM 106
  • 288. • In mixed nerves, there is the appearance of multiple peaks in the action potential. • The multipeaked action potential is called a compound action potential. DEPT. OF PHYSIOLOGY, GMCM 107 2. Compound action potential
  • 289. DEPT. OF PHYSIOLOGY, GMCM 108
  • 290. • Asynchronous discharge of the various fibers • Different conduction velocities DEPT. OF PHYSIOLOGY, GMCM 109
  • 291. DEPT. OF PHYSIOLOGY, GMCM 110
  • 292. WBC and Nerve Lecture Feedback (google.com) DEPT. OF PHYSIOLOGY, GMCM 111
  • 294. DEPT. OF PHYSIOLOGY, GMCM 1 Q
  • 295. Short Essay (8 marks) 1. Explain chronaxie, rheobase, utilization time. Draw strength duration curve. Write briefly (4 marks) 2. Ionic Basis of Resting membrane potential. 3. Ionic Basis of Action Potential. 4. Absolute Refractory Period. Q - KUHS Mar 2021, May 2022 Q - KUHS Feb 2022, May 2022 Q - KUHS July 2022 Q - KUHS Feb 2016
  • 296. Physiological Basis (2 marks) 1. Wallerian Degeneration 2. Sodium Potassium pump helps to maintain RMP. Draw and Label 1. Action Potential in a Nerve 2. Multipolar Neuron Q - KUHS July 2022 Q - KUHS Jan 2019 Q - KUHS Nov 2020, Sep 2021 Q - KUHS Aug 2015