Excitable Tissues-Nerves

1. NERVE PHYSIOLOGY
DISSI GAMBO MAHDI

2. INTRODUCTION
• Excitable tissues are tissues that when stimulated
produces a response - an electrical signal called action
potential
• Excitability is the physiochemical changes that occur in
a tissue when stimulus is applied
• This leads to its ability to generate an action potential
• The stimulus can be mechanical, chemical or electrical
• Excitable tissues comprises of nerves and muscle
tissues

3. INTRODUCTION
The ability of excitable tissue to generate and
propagate action potentials depends upon the
electrical properties of the cell membrane at
rest (Resting membrane potential).

4. NERVE PHYSIOLOGY
• Neurons are Specialized cells that can respond
to stimuli (such as touch, sound, light, and so
on), conduct nerve impulses, and
communicate with each other (Synapse) and
with other types of cells like muscle cells
(Neuromuscular junction).
• Human NS contain >100 billion neurons
• 50-100 times this number are glial cells

5. NEURON
• Structural and functional unit of nervous system
• Similar to other cell in body having nucleus and most
organelles in cytoplasm
• Different from other cells:
I. Neurons have branches or processes
II. Neurons have no centrosome
III. Nissl bodies are confined to cytoplasm and part of
axons
IV. Neurofibrillae
V. Possess axon Hillock

6. NEURON
MYELIN SHEATH
• Many neurons (but NOT all) are insulated with a layer
of Myelin (lipoprotein sheath),
– by Oligodendrocytes in the CNS and
– by Schwann cells in peripheral nerves.
• There are gaps in the myelin sheath known as Nodes of
Ranvier.
• Function of myelin sheath include
– Faster conduction; myelinated axons conduct up to 50 times
faster than the fastest unmyelinated fibers.
– Insulating capacity

7. NERVE

9. THE NEURON

10. THE NEURON

11. CLASSIFICATION OF NEURONS
• Based on the number of poles; unipolar
(embryonic life), bipolar (bipolar cells of
retina) and multipolar.
• Based on function; motor neurons (efferent
nerve) and sensory neurons (afferent nerve)
• Based on the length of axon; Golgi Type I
neurons (long axons) Golgi type II neurons
(short axons)

12. CLASSIFICATION OF NERVE FIBERS
Based on diameter and speed of conduction of
impulse (Erlanger- gasser classification). They are
classified into three major groups:
• Type A nerve fibers (Myelinated spinal nerves)
– Aα or Type I nerve fibers
– Aβ or Type II nerve fibers
– A or Type II nerve fibers
– A or Type III nerve fibers
• Type B nerve fibers (Myelinated preganglionic N)
• Type C nerve fibers or Type IV nerve fibers (sensory
fibers of peripheral and postganglionic autonomic N)

13. MAMMALIAN NERVE FIBER TYPES
Fiber Type Fiber
Diameter (μm)
Conduction
Velocity (m/s)
A - α (Proprioception; somatic motor) 13 - 20 70 - 120
A – β (Touch, pressure) 6 - 12 30 - 70
A - γ (Motor to muscle spindles) 3 - 6 15 - 30
A - δ (Pain, cold, touch) 2 - 5 12 – 30
B (Preganglionic autonomic fibres) 1-2 3 - 15
C (Pain, temperature, Postganglionic
sympathetic fibres)
0.3 – 1.3 0.5 – 2.0

14. NEURAL SUPPORTING CELLS (GLIAL CELLS)
Glial cells provide structural and functional support for
neurons.
There are two major classes’ of glial cells
• Microglia: are present in the CNS and are of macrophage
lineage (they are fixed macrophages) and act as
phagocytic scavengers for defense.
• Macroglia:
– Astrocytes: found throughout the brain. They are involved in
formation the blood-brain barrier and produce Neurotrophins.
– Oligodendrocytes: myelinate neurons in CNS.
– Schwann cells: myelinate neurons in PNS and are pohagocytic
– Satellite cells. Found in PNS, help in support and regulation of
chemical environment of the PNS neurons.

15. DEGENERATION AND REGENERATION OF NEURONS
A. Degeneration
– Anterograde degeneration: if an axon of a neuron is
destroyed, that part of the axon disconnected from the cell
body degenerates. (Wallerian degeneration)
– Retrograde degeneration: The part of the axon that
remains connected to the cell body may degenerate.
B. Regeneration
– Sometimes the regeneration of the neuron occurs
depending on the degree of the injury; if the soma is not
destroyed, the axon sends out sprouts, that will grow,
reestablish the synaptic contacts and re-innervate the
peripheral tissues.

16. Neurotrophins – Neurotrophic Factors
• Are Protein substances that play important role in
growth and functioning of nervous tissue
• Secreted by many tissue in body e.g., muscles/
neurons/ astrocytes
• Functions:
– Facilitate initial growth and development of nerve cells
in CNS & PNS
– Recently – neurotrophins capable of making damaged
neuron re-grow
• used in reversing the devastating symptoms of nervous
disorders like Parkinson disease, Alzheimer's disease,

17. Types of neurotrophins
• 1st
protein identified as neurotrophin- nerve
growth factor (NGF)
• Now many numbers neurotrophin identified
1. Nerve growth factors (NGF)
2. Brain derived neurotrophic growth factor (BDGF)
3. Fibroblast growth factors:
4. Glial cell line- derived neurotrophic factor
(GDNF)
5. Insulin like growth factor I (IGF-I)
6. Fibroblast growth factor

18. PROPERTIES OF NEURONS
Excitability
Adaptation/accomodation
Conductivity
Infatiguability
All or none principle

19. EXCITABILITY
• Ability of a nerve fiber to respond to stimulus.
Is an electrical phenomenon which leads to
generation of action potential. The action
potential can be measured in millivolts

20. Excitation
The stimulus may be electrical, chemical or
mechanical.
• Two types of potentials may be produced
– Local (Non-propagated action potential ) named
after its location synaptic, generator or electronic
potential
– PROPAGATED ACTION POTENTIAL (nerve impulse).
• Both are due to changes in the conduction of
ions across the cell membrane that are
produced by alternations in the ion channels

21. ADAPTATION
• While stimulating a nerve fiber continuously, the
excitability of the nerve fiber is greater in the
beginning. Later the response decreases slowly and
finally the nerve fiber does not show any response
at all.
• When a nerve fiber is stimulated continuously,
depolarization occurs continuously. Continuous
depolarization inactivates the sodium pump and
increases the efflux of potassium ions.

22. CONDUCTIVITY
•Conductivity is the ability to transmit the action potential.
•Action potentials are propagated as waves of depolarization and
repolarization.
•Nerve fibre conduct AP generated from one point to another. It
conducts from cell body to axon direction (one way conduction)
•The action potential propagates differently in myelinated and
unmyelinated nerve fibers.
– In unmyelinated axons - AP propagates in both directions, in
a continuous type of conduction. Therefore, the conduction rate is
relatively slow and more energy consuming.
– In myelinated axons - AP "jumps" from node to node = Saltatory
conduction. Saltatory conduction is both faster and more energy
efficient than conduction in unmyelinated axons.

23. INFATIGABILITY
• Nerve fiber doesn’t become fatigued as it
conducts only one impulse at a time due to its
refractive period

24. REFRACTORY PERIOD
Refractory period is the period at which the nerve does
not give any response to a stimulus. This refractory
period is divided into
• Absolute refractory period, corresponding to the
period from the time the firing level is reached until
repolarization is about one-third complete. No
stimulus, no matter how strong, will excite the nerve.
• Relative refractory period, after two-thirds of
repolarization is complete to the start of after-
depolarization. During this period, stronger than
normal stimuli can cause excitation.

25. RECEPTORS
• Information about the internal and external
environment reaches the CNS via a variety of
sensory receptors. These receptors are transducers
that convert various forms of energy in the
environment into action potentials in neurons.
• CLASSIFICATIONS OF RECEPTORS: generally,
receptors are classified into two
1. Exteroceptors; give response to stimuli arising from
outside the body.
2. Interoceptors; give response to stimuli arising from
within the body.

26. Exteroceptors
They are divided into three groups
• Cutaneous receptors; receptor situated in the skin.
– Touch – meisnner’s corpuscle and merkel’s disk
– Pressure – pacinian corpuscle
– Cold – krause’s end bulb
– Warmth – raffini’s end organ
– Pain – free nerve ending
• Chemoreceptors; respond to chemical stimuli
– Taste - taste buds
– Smell - olfactory cells
• Teleceptors; give response to stimuli arising away from the
body
– Vision - rods and cones in retina
– Hearing - hair cells in organ of corti

27. Interoceptors
They are of two types
• Visceroceptors; receptors situated in the viscera
– Stretch receptors – heart
– Baroreceptors – blood vessels
– Chemoreceptors – GIT
– Osmoreceptors – urinary tract and brain
• Proprioceptors (position of the body in space)
– Muscle spindle – muscles
– Golgi tendon organ – tendon
– Pacinian corpuscles – ligament
– Free nerve endings – fascia and joint
– Hair cells – vestibular apparatus

28. PROPERTIES OF RECEPTORS
1. Specificity of response refers to the response
given by a particular type of receptors to a
specific sensation (muller’s law).
2. Adaptation; it is the decline in discharge of
sensory impulses when a receptor is
stimulated continuously with constant
strength.
– Phasic receptors; get adapted rapidly e.g. touch
and pressure receptors
– Tonic receptors; adapt slowly e.g. pain and cold
receptor

29. RESTING MEMBRANE POTENTIAL (RMP)
• Resting membrane potential is the electrical
potential difference (voltage) across the cell
membrane (between inside and outside)
under resting condition.
• It is the net electrical potential that exist
across the cell membrane of an excitable cell
at rest.

30. The Excitable Cell Membrane at Rest
• When a cell with an excitable membrane is not
transmitting impulses it is said to be at rest.
• The difference in electrical charge across the
membrane is called the Resting Membrane
Potential.
• The Action Potential is simply a brief reversal
(around 1/1000 of a second) of this situation so
that the inside of the cell becomes positive with
respect to the outside.

31. FACTORS MAINTAINING RMP
• The development and maintenance of resting
membrane potential depends on
– Sodium-potassium pump; is an electrogenic pump that
actively moves three sodium ions out of the cell and
two potassium into the cell by using energy from ATP.
– selective permeability of cell membrane; Leak channels-
in resting condition almost all the K+ leak channels are
open but most of the Na+ leak channels are closed.
– The Donnan effects; Refers to the fact that negatively
charged protein ions are held on inside, accumulating
on the inner surface of the membrane and contributing
to its negative electric charge.

32. 32
Resting Membrane Potential
The development and maintenance of RMP is carried out
by movements of ions, which produces ionic imbalance
across the cell membrane.
• 80% caused by selective permeability of the cell
membrane: Leak channels- The K+ diffuses out the cell &
Na+ diffuses inside the cell according to concentration
gradient until when equilibrium is reached. The K+
permeability is 50-75 folds more than Na+
• 20% is caused by the Na+ K+ pump: is an electrogenic
pump that uses energy from ATP.
• The Donnan effect: negatively charged protein ions are
held inside the cell, thus contributing to its negative
electric charge.

33. Contribution of the Potassium Diffusion Potential.
• Assume that the only
movement of ions
through the
membrane is diffusion
of potassium ions
• The ratio of potassium
ions inside to outside
is 35:1,
• the Nernst potential
corresponding to this
ratio is –94 mV

34. Contribution of Sodium Diffusion Through the Nerve
Membrane.

35. Contribution of the Na+-K+ Pump
• The Na+-K+ pump
continuously pumps three
sodium ions to the outside
for each two potassium
ions pumped to the inside.
• This creates an additional
degree of negativity (about
–4 millivolts)
• Therefore, the net
membrane potential with
all these factors operative
at the same time is about –
90 mV.

36. Gated Channels
•Gates can be chemically opened by
neurotransmitters
•Gates can be opened via signal transduction
mechanisms linked to neurotransmitter binding
to receptor
•Gates can be opened by stretch, pressure, etc.

37. Voltage-Gated Sodium Channels
The necessary actor in causing both depolarization and
repolarization of the nerve membrane during the action
potential is the voltage-gated sodium channel

38. Voltage-Gated Potassium Channel
A voltage-gated potassium channel also plays an
important role in increasing the rapidity of
repolarization of the membrane.

39. RESTING MEMBRANE POTENTIAL

40. RESTING MEMBRANE POTENTIAL

41. RESTING MEMBRANE POTENTIAL

42. R RESTING MEMBRANE POTENTIALS r various cell types
Cell types
Skeletal mm
Smooth mm
Neurons
Resting potential
-85 to -95 mV
-50 to -60 mV
-60 to -90 mV

43. ELECTROTONIC POTENTIAL
• Electrotonic potential or local response is a non-
propagated local potential that develops in the nerve
fiber when subliminal stimulus is applied. The sub-
threshold stimulus does not produce action potential,
but produces a slight depolarization called local
response.
• It doesn’t obey all or none law
• It can be summated to generate an action potential
• This local response can be:
– Excitatory function leading to generation of EPSP
– Inhibitory function leading to IPSP

44. EXCITATORY POSTSYNAPTIC POTENTIAL (EPSP)
• Is a non propagated electrical potential that develops
during synaptic transmission.
• When the action potential reaches the pre synaptic axon
terminal, Voltage-gated calcium channels at the pre-
synaptic membrane open.
• The calcium ions enter the axon terminal from ECF and
cause release of neurotransmitter substance from the
vesicles

45. EXCITATORY POSTSYNAPTIC POTENTIAL (EPSP)
• Neurotransmitter, which is excitatory in function
passes through pre synaptic membrane and
synaptic cleft and reaches the postsynaptic
membrane.
• The neurotransmitter binds with receptor protein
present in postsynaptic membrane to form
neurotransmitter receptor complex.
• The neurotransmitter-receptor complex causes
opening of ligand ­
gated channels resulting to influx
of cation (e.g Sodium)

46. EXCITATORY POSTSYNAPTIC POTENTIAL (EPSP)
• Since the sodium ions are positively charged, the
resting membrane potential of the cell is altered
and local depolarization develops.
• This type of local depolarization is called EPSP.
– It is a local potential (response) in the synapse.
– It can be summated to generate an action potential
when the firing threshold is reached

47. INHIBITORY POST-SYNAPTIC POTENTIAL (IPSP)
• Inhibition of synaptic transmission is classified
in to:
• Postsynaptic or direct inhibition
• Pre-synaptic or indirect inhibition
• Negative feedback or Renshaw cell inhibition

48. ACTION POTENTIAL
• Is a transient reversal of the resting membrane
potential
• A rapid change in membrane potential that occurs
when a nerve cell membrane is stimulated.
• The nerve goes from resting (-70) to slightly
positive (+35) in a very short time( few milli
seconds).
• It transmits nerve signal and spread rapidly along
the nerve fiber.

49. The main physiological characteristics of the
AP
1. Obeys the law of "all or nothing." This means
that:
– AP occurs when the stimulus, the power which is
no less than certain thresholds;
– Physical characteristics of the AP (amplitude,
duration, shape) does not depend on the power
of stimulus.
2. Conductivity
3. AP accompanied with refractory period.

50. AP

51. Plateau in some AP

53. DEPOLARIZATION
• Loss of the normal RMP (polarized) state due
permeability of the membrane to Na ions.
• Na+ enters the cell and neutralizes the polarized
state causing membrane potential to depolarize
and move towards positive potential.
• May pass the zero and over shoot to +35mv
• Mostly occurs due to opening of voltage gated
Na channels

54. DEPOLARIZATION

55. REPOLARIZATION
• Rapid reversal of the depolarization state
• It restores the normal polarized RMP
• It occurs due to closure of voltage gated
sodium channels & opening of K+ voltage
gated channels.
• This results to efflux of K+ out of the cell thus
repolarizing the membrane.

56. REPOLARIZATION

57. HYPER POLARIZATION
• Is the lowering of the potential to less than
the RMP
• As a result of continual opening of K channels
after the RMP has been reached.

58. REFRACTORY PERIOD
Refractory period is the period at which the nerve does
not give any response to a stimulus. This refractory period
is divided into
• Absolute refractory period, corresponding to the period
from the time the firing level is reached until
repolarization is about one-third complete. No stimulus,
no matter how strong, will excite the nerve.
• Relative refractory period, from about one-third
completed repolarization and extends through rest of
the repolarization period. During this period, stronger
than normal stimuli can cause excitation.

59. Dentistry 07 59
FUNCTIONS OF ACTION POTENTIALS
• Information delivery to CNS
– carriage of all sensory input to CNS. Consider block APs
in sensory nerves by local anaesthetics.
• Information encoding
– The frequency of APs encodes information
• Rapid transmission over distance (nerve cell APs)
– Note: speed of transmission depends on fiber size and
whether it is myelinated.
• In non-nervous tissue APs are the initiators of a range of
cellular responses
– muscle contraction
– secretion (eg. Adrenalin from chromaffin cells of medulla)

60. PROPAGATION OF AP
• Leads to nerve impulse transmission
• Occurs differently in myelinated and un-
myelinated fibers
– MYELINATED FIBRES
• Through saltatory method
• Jumps from one node of ranvier to another
• Faster and less energy consuming

61. PROPAGATION OF AP

62. PROPAGATION OF AP
• UN MYELINATED FIBRE
– Point by point conduction across the fiber
membrane
– Slower and more energy consuming

63. PROPAGATION OF AP

64. SYNAPSE
• Impulses are transmitted from one nerve cell to another cell at
synapses. These are the junctions where the axon or some other
portion of one cell (the presynaptic cell) terminates on the dendrites,
soma, or axon of another neuron or in some cases a muscle or gland
cell (the postsynaptic cell).
CLASSIFICATION OF SYNAPSE
• Anatomical classification;
– Axoaxonic synapse
– Axodendritic synapse
– Axosomatic synapse
• Functional classification;
– Electrical synapse; there is direct physiological continuity and ionic exchange
between the presynaptic and postsynaptic neurons, separated by gap junction.
– Chemical synapse; is the junction between a nerve fiber and a muscle or
between two nerve fibers through which signals are transmitted by the release
of chemical transmitter.

65. Chemical SYNAPSE

67. PROPERTIES OF SYNAPSE
• One way conduction– In chemical synapse,
impulses are transmitted in one direction while it
can be the reverse in electrical synapse.
• Synaptic delay
• Fatigue ; due to depletion of neurotransmitter
• Summation
– Spatial summation: many presynaptic excitatory
terminal simultaneously stimulate postsynaptic neurons
– Temporal summation: repeated stimulation of one
presynaptic terminal.

68. SYNAPTIC transmission
Mechanism of excitatory nerve nerve synaptic transmission
‐
1. Pre synaptic AP depolarizes the terminal knob
‐
2. Opens voltage gated Ca2+ channels
‐
3. Vesicles of transmitter migrate to pre synaptic membrane and
‐
burst.
4. Transmitter crosses cleft and attaches to receptors on post‐
synaptic membrane
5. These receptors are bound to ligand gated channels
‐
6. Opening of sodium channels and influx of sodium ions from ECF
7. Development of excitatory postsynaptic potential
8. Opening of sodium channels in the initial segment of axon
9. Influx of sodium ions from ECF and development of action
potential
10.Spread of action potential through axon of postsynaptic neuron

69. Applied Physiology
• Local Anaesthsia
• Spinal shock
• Stroke