1. Edris A. 1
Membrane Potential
&
Electrical Signaling of Neuron
By
Idris Ahmed (Lecturer)
samsonphld@gmail.com
2. • Objectives
• At the end of this session students will expected to:
• Define membrane potential
• Describe causes of resting membrane potential.
• List types of ion channel with their functions.
• Explain graded potential & action potential
• Describe changes in ionic channels for action potential
• Name types of excitable tissue and their functions.
• Describe brief anatomy of neuron
• Describe types of synaptic transmission
Edris A. 2
3. Edris A. 3
• Membrane Potential is electrical potential (voltage
difference) that exist across the cell membranes (voltage
difference b/n Intracellular & Extracellular environment).
• It is found in all cells of the body.
• It is caused by ions (charge) concentration difference on the
two sides of the cell membrane.
– (unequal distribution of ions across cell membrane).
• Thus ICE is relatively -ve while ECE is relatively +ve
•
4. Edris A. 4
• The contributing factors for –Ve ICE & +Ve ECE
are:
• 1. Unequal distribution Ions b/n intracellular side &
exrtacellular side of plasma membrane. (Na+ & K+)
– E.g. [Na+] is (142mEq/L) out side cell but 14mEq/L
inside cell, [K+] is (140mEq/L) inside cell but 4 mEq/L
outside cell.
– Further more Plasma membrane is impermeable to Na+
but slightly permeable to K+.
– As a result, K+ is constantly leaking out of the cell.
– In other words, positive charge is constantly leaking out
of the cell.
6. Edris A. 6
• 2.The Na+/K+ pump is constantly pumping 3 Na+
ions out and 2 K+ ions in for every ATP used. Thus
more positive charge is leaving than entering.
• 3.There are protein anions (i.e., large negatively
charged proteins) within the cell that cannot travel
through the plasma membrane.
• .
7. • The diffusion potential (Nernst potential ) is the force
which exactly opposes the net diffusion of a particular ion
through the membrane .
• It is determined by the ratio of particular an ion
concentration inside to concentration outside cell,
• The greater this ratio, the greater tendency for the ion to
diffuse & greater the Nernst potential required to prevent
additional net diffusion.
• Nernst equation,
• EMF is electromotive force.
Edris A. 7
8. • When a membrane is permeable to several different
ions, the diffusion potential depends on 3 factors:
– (1) the polarity of the electrical charge of each ion,
– (2) the permeability of the membrane (P) to each ion, and
– (3) the concentrations (C) of the ions inside (i) & outside
(o) of the membrane.
Edris A. 8
9. • Goldman equation, gives the calculated membrane
potential inside of the membrane when Na+, K+ &
Cl–, are involved..
• Goldman equation
Edris A. 9
10. • Nerve and muscle cells, are capable of generating
rapidly changing electrochemical impulses(Action
potential) at their membranes.
• These impulses are used to transmit signals along
the nerve or muscle membranes.
• In other types of cells like gland cells, macrophages
...etc local changes in membrane potentials (graded
potential) activate many cellular functions.
Edris A. 10
11. Edris A. 11
Resting Membrane Potential(RMP).
• At resting condition
– no external stimulus
– Ion channels are in a closed state
– No net flow of ions
– thus cells maintain –ve ICE and +ve ECE known as
RMP.
• RMP is property of all living cells
• Cell with RMP is said to be in a polarized state.
12. Edris A. 12
• Example:-
Type of Cell RMP
Neuron -90 mv
Sekeletal muscle -80 mv
Cardiac muscle -90mv
Smooth muscle -40mv to -60mv
13. Edris A. 13
• However RMP of cells can be disturbed due to
influx or efflux of ions (charges) through gated ion
channels.
• Ion channels are complexes membrane protein.
•
• These channels are normally closed,
– but open in response to appropriate & sufficient stimulus
– Then allow flow of specific ions into or out of the cell.
14. Edris A. 14
• Different types of Ion channels present in cell
membrane:
• 1. Ligand-gated ion channel
• Open in response to hormone, neurotransmitter or
other chemicals.
• Eg. Cholinergic Nicotinic Receptor at
neuromuscular junction. Open by binding of 2 Ach
molecules on its alpha subunits to allow influx of
Na+
15. August 29, 2023 Edris A. 15
• Ach receptor (pentameric nicotinic receptor).
– 2α: 1β: 1γ: 1δ subunits
16. Edris A. 16
• Ligand gated ion channel.
– Ionotropic
– Metabotropic
17. Edris A. 17
• 2. Voltage-gated ion channel
• Open in response to change of electrical potential
(membrane potential)at the cell membrane.
• These are found in the excitable tissues (Nerve &
Muslce)
• Eg.
• Voltage gated Na+ channel
• Voltage gated K+ channel
• Voltage gated Ca++ channel
19. Edris A. 19
• 3. Mechanically-gated ion channel
– Open in response to mechanical stimulus like stretch or
pressure..
– When a channel is open, its specific ion(s) will enter or
exit depending on their electrochemical gradient.
– Na+ channel in mechanoreceptors
• 4. Leaky ion channel:
– Always remain open & allow passage of ions that fit to
its pore size. Eg. Leaky K+ channel
20. Edris A. 20
• The voltage gated Na+ channel.
– It has two gate controls( M-o & H-i)
21. Edris A. 21
• Measurement of Membrane Potential
• The potential difference between an ICE and ECE measured in
voltmeter and expressed in millivolts (mV).
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Graded potential.
• It is local electrical disturbance
• Propagate like wave in all direction
• Its propagation is decreasing (as it goes away from point
of origin it amplitude decrease)
• Its amplitude depend on strength of stimulus
• Strong stimulus generated large graded potential that
can propagate longer distance before it disappears,
• Occurs in dendrite, cellbody or motor end plate
– b/c these parts lacks voltage gated ion channel
• If it reaches threshold potential it generate action
potential.
23. Edris A. 23
• Sub-threshold stimulus do not generate action potential (weak
stimulus, potential less than threshold, not generate action
potential).
• Threshold is minimum required potential to generate action.
potential
24. Edris A. 24
• Weak stimulus cause opening of few ion
channels.
• Influx of few ions- little disturbance- easily
disappear-with out causing action potential.
• Strong stimulus cause opining of many ion
channels.
• Influx of many ions- large disturbance-not easily
disappear-propagate longer distance-if it reaches
threshold point initiate action potential.
25. Edris A. 25
Action potential (AP)
• It is rapid reversal of MP from –Ve to +Ve then to –Ve.
• It propagate with out decreasing
• Amplitude not vary with strength of stimulus but its frequency
• Occurs only in excitable tissue-nerve & muscle
• b/c these have voltage gated ion channel
• Only threshold stimulus can generate AP
• Consume ATP energy for Na+ out flow by Na+/K+pump.
• Stages of AP are
• Resting stage
• Depolarization stage
• Repolariztion stage
• Hyperpolarization stage
26. Edris A. 26
• Events in different stages of action potential.
28. Edris A. 28
• Threshold for Initiation of the Action Potential.
• An action potential will not occur until initial rise in membrane
potential is large enough to create vicious cycle of action potential
• This occurs when the number of Na+ ions entering the fiber becomes
greater than the number of K+ ions leaving the fiber.
• A sudden rise in membrane potential of 15 to 30mv usually is
required.
• Therefore, a sudden increase in the membrane potential in a large
nerve fiber from –90 mv up to about –65 mv usually causes the
explosive development of an action potential.
• This level of –65 millivolts is said to be the threshold for stimulation.
29. Edris A. 29
• Effect of stimuli of increasing voltages to elicit an action potential.
Note development of “acute subthreshold potentials” when the
stimuli are below the threshold value (A & B).
31. • Some action potential has plateau phase
• Plateau phase is when membrane potential remain in a
depolarized state for short time.
• It is due to influx of Ca++ via slow Ca++ channel
(thus K+ efflux=Ca++ influx)
• Plateau phase help to increase force of contraction by
supplying Ca++ and to prevent tetanisation.
• Eg. Action potential of cardiac muscle and uterus wall
smooth muscle
Edris A. 31
32. • Plateau phase of cardiac muscle action potential
Edris A. 32
33. All or non principle of Action potential
• Once an action potential has been elicited at any
point on the membrane of a normal fiber,
– the depolarization process travels over the entire
membrane if conditions are right,
– it does not travel at all if conditions are not right.
• This is applied to all normal excitable tissues..
Edris A. 33
34. Refractory Period
• It is time period when new action potential cannot occur in
an excitable fiber as long as the membrane is still
depolarized from the preceding action potential.
• The reason for this is that shortly after the action potential
is initiated, the sodium channels (or calcium channels, or
both) become inactivated,and No amount of excitatory
signal applied to these channels at this point will open the
inactivation gates.
Edris A. 34
35. • The only condition that will allow them to reopen is when
membrane potential return to original resting membrane
potential level.
• Absolute refractory period time when the second action
potential cannot be elicited, even with a strong stimulus is
applied. ( 1/2500 second for large myelinated nerve fibers).
Edris A. 35
36. Local Anesthetics.
• Many substances used clinically as local anesthetics
procaine and tetracaine.
• Most of these act directly on the activation gates of the
sodium channels.
• They make activation gate more difficult to open thus
reducing membrane excitability.
• Nerve impulses fail to pass along the anesthetized nerves.
Edris A. 36
37. Edris A. 37
Excitable tissues
• Excitable tissues are those which receive a stimulus and
respond to a stimulus by forming Action potential.
• The electrical impulse (action potential) that travels along
their plasma membrane.
• In our body Nerve & muscle are excitable tissues.
• They can produce electrical signals (action potential) when
stimulated to threshold.
• Because they have voltage gated ion channel.
• These impulses are used to transmit signals along the nerve
or muscle membranes.
38. Edris A. 38
Nerve tissue
• Coordinate body activities by Electrochemical signals
– Electro- electrical signal- (action potential)
– Chemical signal- neurotransmitters
• Although nervous system is very complex, there are
only two main types of cells in nerve tissue.
• Neuron - actual nerve cell
• Neuroglia or glial cell- supporting cells
39. Edris A. 39
The neuron
• is the "conducting" cell that transmits impulses.
• Specialized to generate & conduct information
(electrochemical signal) from one part to another
part of the body. .
• Therefore it is the functional and the structural
unit of the nervous system.
• Neurons are also amitotic-do not replicate by
mitosis.
40. Edris A. 40
• Parts of neuron.
Dendrite
Cell body-soma
Axon hillock
Axon
Collateral
Axon terminal
41. Edris A. 41
Dendrites
• are thin branched finger like projections from the soma to
receive incoming signals.
• Their number varies among neurons
• They effectively increase the surface area of a neuron for
signal reception.
• Convey information towards the soma by graded
potentials
• Have no voltage regulated ion channel-not generate
Action potential
42. • Proximal part of dendrites (near the cell body) contain Nissl
bodies and parts of the Golgi apparatus
however, the main cytoplasmic organelles in dendrites
are microtubules and neurofilaments
• The number of dendrite determines ones intelligence Vs
mental retardation
a person with high number of dendrites has better
intelligence as compared with those with few
dendrites
Functions of dendrite :
– receive the input signal from other neurons and transfer it
in to the cell body(i.e. they are input regions)
– they increase surface area for signal transmission (90%
surface area) Edris A. 42
43. Edris A. 43
Cell body (soma or perikaryon)
• It is the site of origin for axon and dendrites
• Contains nucleus & other organelles- biosynthetic center
of the neuron.
• It has Nissl bodies (stacks of rough endoplasmic reticulum)
and prominent Golgi apparatus for synthesis of
neurotransmitters & cellular materials.
• It contain cytoskeletal elements like microtubules,
microfilaments & neurofilaments
44. Edris A. 44
• Cell body contains many bundles of protein
filaments (neurofibrils) which help maintain the
shape, structure, transport and integrity of the cell.
• Not carry out mitotic division(amitotic).
• Cell body do not have voltage gated ion channel- not
generate action potential.
• Receive stimulus by graded potential
45. Edris A. 45
• Nuclei -clusters of cell bodies in the CNS
• Ganglia- clusters of cell bodies in the PNS
• Functions of cell body:
– Reception of signal by graded potential
– Synthesis of material for nerve function
– Summation of signals- receive different signal,
add up and pass net result to axon.
46. Edris A. 46
Axon hillock
• point of origin for axon
• It is where the first voltage gated ion is found
• It has high density of voltage-gated ion channels of Na+, K+,
Ca2+ threshold for AP
• Thus where the first action potential is generated in the
neuron it threshold potential is reached.
47. Edris A. 47
Axon
• Most neurons have a single axon – a long (up to 1m)
process to convey information away from the cell body.
• Originates from a special region of cell body- axon hillock.
• Transmit action potential from the soma toward axon
terminal where they cause Neurotransmitters release.
• Axolemma = axon plasma membrane.
48. Edris A. 48
• Some axons are surrounded by a myelin sheath, a wrapping
of lipid which:
Protects the axon and electrically isolates it
Increases the speed of AP transmission
• The myelin sheath wrapping is not continuous.
• Along axon there are gaps where there is no myelin – these
are nodes of Ranvier.
• Large number of voltage gated ion channels present
at nodes of Ranvier.
• Action potential do not occur on myelin sheathed part of
axon.
• Thus action potential jumps form one node of Ranvier to the
next node ( saltatory conduction).
49. Edris A. 49
• Often an axon branchs forming collaterals.
– Each collateral may split into telodendria
• Axon terminal (synaptic knob), which contains
synaptic vesicles – membranous bags of
Neurotransmiters.
• Synapse is a gap between axon terminal and
adjacent cell across which a nerve impulse passes
from an axon terminal to a neuron, a muscle cell, or
a gland cell.
50. Edris A. 50
Axon terminal
• Knob like structure at end of axon.
• Contain vessicles filled with neurotransmitters (NT).
• NT are synthesized at cell body and stored at axon terminal.
51. Edris A. 51
Functions of the axon
a. Impulse conduction usually, away from soma with
a speed of 0.5 -120m/s
b. Convey substances toward or away from the
synaptic terminals
• By anterograde transport- the movement of materials is from
the soma (cell body) towards the axon terminal
• By retrograde transport - the movement of material is from
the axon terminal back to the cell body
52. Axonal Transport
• Most axons are too long to allow diffusion of
substances from the soma to the synaptic endings.
• Axonal transport( axoplasmic transport) is a cellular
process responsible for movement of:
mitochondria
lipids and proteins
synaptic vesicles
enzymes between cell body & axon terminal
through axoplasm
• Axonal transport requires metabolic energy and
involves calcium ions.
Edris A. 52
54. 1. Anterograde transport
• It uses a motor protein called kinesin
kinesin carry the material to be transported and
moves down to the axon terminal
Fast anterograde transport moves:
mitochondria
synaptic vesicles
membrane proteins
enzymes such as acetylcholensterase
and small molecules such as glucose and amino acids
• Rates of transport - 200 to 400 mm/day
54
56. Slow anterograde- transports occur at a rate of 0.5-
10mm/day
• it moves
enzymes and
cytoskeletal components down the neuron
• Damaged nerve fibers in the peripheral nervous
system regenerate at a speed governed by slow
axonal transport
56
58. 2. Retrograde axonal transport
• Returns used synaptic vesicles and other materials to the
soma
• Uses the motor protein dynein ( dynein carry the materials
to be transported from the axon terminals back to the cell
body.
• Purposes of retrograde transport:
for degradation
for regulation of gene expression
to the Golgi complex for repackaging
some pathogens use this process to invade the CNS
E.g. tetanus toxin ,herpes simplex virus ,rabies ,polio viruses
58
59. Edris A. 59
Neuroglia (Glial cells )
• provide a support for the neurons
• Neuroglia cells do not conduct nerve impulses, however,
they support, nourish, and protect the neurons.
• They are far more numerous than neurons - unlike neurons
they are capable of mitosis (replicate by mitosis)-
responsible for brain tumor.
• There are several types of glial cell in the nervous
system:
1. Astrocytes
2. Microglia
3. Oligodendrocytes
4.Ependymal cells
5.satellite cells
6. Schwann Cells
60. Edris A. 60
1. Astrocytes
• They are most abundant and versatile glial cells
• Have numerous processes to support branching neuron.
• Anchor neuron to the capillary blood supply.
– From blood brain barrier- protection of neuron from toxin
• restricts the type of substances that can enter the brain.
– facilitate nutrient delivery to neuron ( blood astrocyte
neuron)
• Control chemical environment around neuron-act as K+ &
Neuro transmitter buffer
– Uptake of K+ and Neuro transmitter
• Guide the migration of developing neuron.
61. Edris A. 61
2. Microglia
• are small ovoid cells of CNS
• Have long thorny process
– The process touch near by neuron-check vitals
• Specialized immune cells of CNS-act as
macrophage to engulf debris & microbs.
• This is because immune cells can not enter to CNS
• Therefore remove cellular waste products and
protect neurons against microorganisms(pathogens).
62. Edris A. 62
3. Oligodendrocytes
• have many dendrites.
• Found in central nervous system structures
• Function is to wrap neuronal axons that form an
insulating coat known as the myelin sheath.
• Myelin sheath also increase speed of action potential
conduction along axon-by saltatory conduction.
63. Edris A. 63
4. Ependymal cells
• Are low columnar epithelial cells.
• They line ventricles of brain and central canal of
spinal cord.
• Some are ciliated to facilitate movement of
cerebrospinal fluid (CSF).
5. satellite cells
• encapsulate dorsal root & cranial nerve ganglia(i.e.
it supports ganglia)
• Regulate the exchanges of materials between
neuronal cell bodies(ganglia) and interstitial fluid.
64. Edris A. 64
6. Schwann Cells
• are peripheral nervous system structures that wrap
some neuronal axons to form an insulating coat
known as the myelin sheath.
• Oligodendrocytes & Schwann cells indirectly assist
in the conduction of impulses as myelinated nerves
can conduct impulses faster than unmyelinated
ones.
• The white matter in the brain gets its color from a
large number of myelinated nerve cells.
65. Edris A. 65
• The formation of a myelin sheath around a peripheral axon
66. Edris A. 66
• Formation of myelin sheaths in the CNS by an oligodendrocyte.
67. Edris A. 67
• The different types of neuroglial cells.
68. Edris A. 68
Functional Classfication of neurons into three groups:
• Sensory neurons ( afferent neurons) transmit sensory
impulses from the skin, sensory organs or from various
body parts toward the central nervous system (CNS).
– Join spinal cord via dorsal horn
– Their cell body is found out side spinal cord,
• Motor neurons (efferent neurons) transmit nerve
impulses from the CNS toward effectors, target cells
that produce some kind of response.
– Effectors include muscles, sweat glands, and many other
organs.
• Association neurons ( interneurons ) are located in the
CNS (brain and spinal cord)
– transmit impulses from sensory neurons to motor neurons.
– More than 90% of the neurons of the body are association
neurons.
69. Edris A. 69
• Functional Classification of Neurons and Nerves
70. Edris A. 70
Neurons can be classified by structure as :-
• Multipolar neurons have 1 axon & numerous dendrites.
– Function as motor neuron or association ( between
sensory & motor neuron in CNS)
– Most neurons are of this type.
• Bipolar neurons have one axon and one dendrite.
– They emerge from opposite sides of the cell body.
– Bipolar neurons are found only as specialized sensory
neurons in the eye, ear, or olfactory organs.
71. Edris A. 71
• Unipolar neurons have one process of emerging
from the cell body.
– this processes branches in to 2 with T-shape,
– Both processes function together as a single axon.
– Dendrites emerge from one of the terminal ends of the
axon.
– The trigger zone in a unipolar neuron is located at the
junction of the axon and dendrites.
– Unipolar neurons are mostly sensory neurons.
74. Edris A. 74
Propagation of Action potential
1. Salutatory conduction (leaping/jumping):
• It occurs in myelinated axon.
• Action potential jumps from first node of Ranvier to
the next until it reach the axon terminal.
• The speed of conduction is fast(1-120m/s).
• It consume less energy as it use few number of
action potential.
75. Edris A. 75
2. Cable conduction:
• it occurs in unmyelinated axon,
• Speed of conduction is slower,because it need
generation of action potential in every patch of
axon.
• The speed increase with diameter.
• It consume much ATP energy as compared to
salutatory conduction since it use many action
potetnial .
76. Edris A. 76
• Conduction of Action potential.
– Saltatory conduction in myelinated axon
– Cable conduction in unmyelinated axon
77. Edris A. 77
Physiologic Classification Nerve Fibers
• Some signals need to be transmitted to or from the central
nervous system extremely rapidly; otherwise, the
information would be useless.
• The momentary positions of the legs during running must
reach brain rapidly (need fast conducting fibers) .
• Further more prolonged, aching pain, do not need to be
transmitted rapidly, (need slowly conducting fibers).
• The diameter of nerve fibers is b/n 0.5 and 20 micrometers.
• The larger the diameter, the greater the conducting velocity
(nerve conducting velocities range from 0.5 to 120 m/sec).
78. Edris A. 78
General Classification of Nerve Fibers.
• It classifies nerve fibers into types A and C.
Type A fibers
• are further subdivided into α, β, γ, and δ, fibers.
• type A fibers are the typical large and medium-sized
myelinated fibers of spinal nerves.
• Few large myelinated fibers can transmit impulses at
velocities as great as 120 m/sec, ( distance longer than a
football field in 1 second).
79. Edris A. 79
Type C fibers
• are the small unmyelinated nerve fibers that conduct
impulses at low velocities.
• Type C fibers constitute more than one half of the
sensory fibers in most peripheral nerves as well as
all the postganglionic autonomic fibers.
• The smallest fibers transmit impulses as slowly as
0.5 m/sec.
80. Edris A. 80
Alternative Classification Nerve Fibers by
Sensory Physiologists are:
Group Ia
• Fibers from the annulospiral endings of muscle spindles
– ≈17 microns in diameter
– α-type A fibers
Group Ib
• Fibers from the Golgi tendon organs
– ≈ 16 micrometers in diameter;
– α -type A fibers.
81. Edris A. 81
Group II
• Fibers from most discrete cutaneous tactile receptors
and from the flower-spray endings of the muscle
spindles
– ≈8 micrometers in diameter
• β- type A and γ -type A fibers.
82. Edris A. 82
Group III
• Fibers carrying temperature, crude touch, and pricking pain
sensations
– about 3 micrometers in diameter;
– they are δ -type A fibers.
Group IV
• Unmyelinated fibers carrying pain, itch, temperature, and
crude touch sensations (0.5 to 2 micrometers in diameter;
they are type C fibers in the general classification).
83. Edris A. 83
Synaptic Transmission
• Synaptic transmission refers to the propagation of nerve impulses
from one nerve axon terminal to another nerves or muscle cell and
gland cell.
• This occurs at a specialized cellular structure as synapse-junction at
which axon terminal of pre-synaptic neuron terminates at some
location upon postsynaptic neuron.
• The end of a pre-synaptic axon forms terminal button.
• An axon can make contact anywhere along the second neuron:
• on dendrites (an axo-dendritic synapse)-Excitatory,
• On cell body (an axo-somatic synapse)-Inhibitory
• On axons (an axo-axonal synapse)-Modulatory.
84. Edris A. 84
• The axon terminal has two internal structures
– Vesicles filled with neurotransmitter
– Mitochondria
• The mitochondria provide energy for synthesis and release of
neurotransmitters.
• The neurotransmitter has excitatory or inhibitory function on
post synaptic neuron:
– Based on type of transmitter and
– Based on type of receptor.
• Acetylcholine is excitatory on nicotinic receptor.
• Gama amino butric acid (GABA) is inhibitory on post synaptic.
– Activation of alpha-1 receptors bring contraction
– Activation of beta-2 receptors bring relaxation
85. Edris A. 85
• Nerve impulses are transmitted at synapses by
– release of chemicals (neurotransmitters) or
– electrical conduction via gap junction.
• Neurotransmitters are a diverse chemical such as:
• dopamine
• gamma-aminobutyrate (GABA),
• enkephalins.
• Acehtylcholine
• norepinephrine
• Mechanisms of their action are diverse as the different
receptors respond by diverse mechanisms.
86. Edris A. 86
Neurotransmitters:
• are chemicals present in axon terminals of neuron,
– liberated upon stimulation of Neuron
– diffuses across the synaptic gap to stimulate (depolarize)
or inhibit (hyperpolarize) the postsynaptic membrane
87. Edris A. 87
• A substance is classified as a neurotransmitter if it
fulfills four criteria:
1. It is synthesized in the presynaptic neuron
2. It is released in amounts sufficient to exert its action on
the postsynaptic neuron or effectors organ
3. When applied exogenously (as a drug) in reasonable
concentration, it mimics exactly the action of the
endogenously released transmitter.
4. A specific mechanism exists for removing it from its site
of action (in the synaptic cleft).
88. Edris A. 88
Mechanism of Neurotransmitter action.
• Neurotransmitters are:
1. Ionotropic: bring fast effect, open ionic gates and allow
the flow of ions to postsynaptic membrane (eg. Ach)
2. Metabotropic: bring slower effect via activation of second
messenger or metabolic change , longer lasting change,
affecting cellular permeability (using Ca2+, calmodulin,
cAMP) (eg. norepinephrine)
– cAMP: cyclic Adenosine Mono Phosphate
3. Neuromodulators/Neuroregulators: substances that affect
the level of excitation of the postsynaptic membrane
without being NTs themselves.
89. Edris A. 89
• “Second messenger” system by which NT can activate second neuron.
90. Edris A. 90
Attention:
• One NT can bind to many different receptors.
• No two NT bind to the same receptors.
• Different NT are released under different conditions.
• The same NT can have different postsynaptic
actions, depending on type of receptor it binds
– Ach on heart muscle hyperpolarize ↑(K+ efflux)
rhythmic activity, and
– Ach on skeletal muscle rapid depolarization (Na+
infulx) contraction.
91. Edris A. 91
Classes of neurotransmitters
i. Amino acids
ii. Purines (adenosine, ATP). iii. Amines
iv. Gaseous NT (NO, CO) v. Peptides
1. Amino acids NT
• Glycine: inhibitory NT in the spinal cord, retina
• Glutamate: Excitatory NT in cerebral cortex, brainstem
• Aspartate: Excitatory NT in spinal cord
• GABA: Inhibitory NT in cerebellum, retina
93. Edris A. 93
4. Gaseous neurotransmitters
i. Nitric oxide(NO)
• it is a gas that is synthesized from amino acid L-arginine by
nitric oxide synthase.
• NO synthase activates guanylate cyclase, which stimulates
the formation of cyclic guanosine monophosphate(cGMP)
from GTP.
• NO is unique among NT, because not stored in vesicles.
• NO is synthesized as needed & diffuses from the cytoplasm
of the postsynaptic cell.
94. Edris A. 94
• Functions of NO are:
1. Synaptic plasticity in learning and memory (LTP)
2. Local mediator by activating macrophages and neutrophils
(help them to kill & invading microorganisms)
3. Released in autonomic nerves in penis causes local blood
vessel dilation that is responsible for penile erection)
ii. Carbon monoxide (CO)
• In the cerebellar and olfactory neurons (promote adaptation
in olfactory neurons)
• For neuroendocrine regulation of the hypothalamus
• It has similar mechanism with NO
95. Edris A. 95
Types of synapse
1. Chemical synapse
• arrival of action potential at axon terminal cause release of
neurotransmitter that crosses the synaptic space and
produces a new action potential in second nerve cell.
• Synaptic space (synaptic cleft) has with of 200 to 300
angstroms
• It is a one-way communication (only from pre to post
synaptic).
96. Edris A. 96
• At chemical synapses, there is no intercellular continuity,
– thus no direct flow of current from pre- to postsynaptic
cell.
• Synaptic current flows across the postsynaptic membrane
only in response to the secretion of neurotransmitters which
open or close postsynaptic cell ion channels after binding to
receptor molecules
97. Edris A. 97
Components of chemical synapse:
A. Presynaptic neuron - neuron sending the impulse
1. Axon of presynaptic neuron terminates on the soma or
dendritic region of postsynaptic neuron (second neuron).
2. Axon ends in terminal branches with synaptic knobs that
contain many mitochondria and vesicles containing chemical
(neurotransmitter)
B. Synaptic cleft - space between cells across which neurotransmitters
must be transmitted.
– It is about 20-50 nm space.
– No direct connection between presynaptic and postsynaptic.
C. Postsynaptic neuron - neuron receiving impulse.
– It contain receptor for neurotransmitter.
– Neurotransmitters initiate production of the action potential in the
postsynaptic neuron.
98. Edris A. 98
Steps In Chemical Synaptic Transmission
• This transmission involves four main steps.
1. The neurotransmitter must be synthesized and
stored in vesicles at axon terminal so that when an
action potential arrives at the nerve ending, the cell
is ready to pass it on to the next neuron.
2. When an action potential does arrive at the terminal,
the neurotransmitter must be quickly and efficiently
released from the terminal into the synaptic cleft.
99. Edris A. 99
3. The neurotransmitter must then be recognized by selective
receptors on the postsynaptic cell so that it can pass the
signal and initiate another action potential.
• In some cases, the receptors act to block the signals of other
neurons also connecting to that postsynaptic neuron-thus
stop further progress of the signal.
4. After its recognition by the receptor, the neurotransmitter
must be inactivated so that it does not continually occupy
the receptor sites of the postsynaptic cell.
Inactivation of the neurotransmitter
• avoids constant stimulation of the postsynaptic cell and
undesired over activation.
• Also make the receptor free to receive additional
neurotransmitter molecules, when another action potential
arrive..
100. Edris A. 100
• Transmission of impulse at chemical synapse by release of
neurotransmitter from axon terminal of presynaptic to activate/act on/
post synaptic neuron/muscle or gland/.
101. Edris A. 101
Synaptic Delay
• There is a 0.2-0.5 millisecond synaptic delay
between the arrival of action potential at synaptic
knob & its effect on postsynaptic membrane.
• Most of that delay reflects the time involved in
calcium influx and neurotransmitter release.
• The neurotransmitter diffusion across the cleft takes
very little time since synaptic cleft is very narrow.
102. Edris A. 102
• Synaptic Delay is amount of time consumed during
transmission of a neuronal signal from a presynaptic neuron
to a postsynaptic neuron.
• This time is consumed for:
1. Ca++ influx & discharge of transmitter from presynaptic
terminal,
2. diffusion of the transmitter to the postsynaptic neuronal
membrane,
3. action of the transmitter on the membrane receptor,
103. Edris A. 103
4. action of the receptor to increase the membrane
permeability,
5. inward diffusion of sodium to raise excitatory
postsynaptic potential to a high enough level to elicit an
action potential.
• The minimal period of time required for all these events to
take place, is about 0.5 millisecond even when large
numbers of excitatory synapses are stimulated
simultaneously.
104. Edris A. 104
Postsynaptic Potentials
• Postsynaptic potentials are graded potentials that develop in
postsynaptic cell due to neurotransmitter.
• Two major types of postsynaptic potentials develop at
neuron-to-neuron synapses are:
– excitatory postsynaptic potentials and
– inhibitory postsynaptic potentials.
105. Edris A. 105
Excitatory Postsynaptic Potentials (EPSP)
• It is a graded depolarization caused by the arrival of a
neurotransmitter at the postsynaptic membrane.
• An EPSP results from the opening of chemically
regulated ion channels that cause influx of +ve charge
and depolarization.
• Eg. Binding of Ach to nicotinic receptor bring EPSP.
• EPSP affects only the area immediately surrounding the
synapse Because it is a graded potential.
106. Edris A. 106
Mechanisms of Excitation (EPSP)
1. Opening of sodium channels
• to allow large numbers of positive electrical charges to
flow to the interior of the postsynaptic cell.
• This raises the intracellular membrane potential in the
positive direction up toward the threshold level for
excitation (depolarization).
• It is by far the most widely used means for causing
excitation.
107. Edris A. 107
2. Depressed conduction through Cl- or K+ channels,or
both.
• This decreases influx of Cl- to postsynaptic neuron or
decreases efflux of positively charged K+
• Both effects make the internal membrane potential more
positive than normal, which is excitatory.
108. Edris A. 108
Inhibitory Postsynaptic Potentials (IPSP)
• IPSP, is a transient hyperpolarization of the
postsynaptic membrane.
• An IPSP may result from opening of chemically
regulated K+ channels (K+ efflux) or opening of Cl-
channels (Cl- influx).
• Both K+ efflux & Cl- influx bring hyperpolarization to
inhibit action potential generation.
• The neuron is inhibited as hyperpolarization continues
– Larger depolarizing stimulus needed to reach
threshold
109. Edris A. 109
• Excitatory & Inhibitory Post Synaptic Potential.
110. Edris A. 110
Presynaptic Inhibition and Facilitation
• An axo-axonal synapse that occurs on synaptic knob can
modify rate of neurotransmitter release from
presynaptic membrane.
In presynaptic inhibition,
• GABA release inhibits the opening of voltage-regulated
Ca++ channels in the synaptic knob.
• This inhibition reduces amount of NT released at the
synaptic knob thus limits effects on the postsynaptic
membrane.
111. Edris A. 111
In presynaptic facilitation,
• activity at an axo-axonal synapse increases amount of
neurotransmitter released when an action potential
arrives at synaptic knob.
• This increase, enhances & prolongs the effects of the
neurotransmitter on the postsynaptic membrane.
• The neurotransmitter serotonin is involved in
presynaptic facilitation.
• In the presence of serotonin released at an axo-axonal
synapse, voltage-regulated calcium channels remain
open for an extended period.
114. Edris A. 114
Effect of Acidosis or Alkalosis on Synaptic Transmission.
• Most neurons are highly responsive to changes in pH of the
surrounding interstitial fluids.
Normally, alkalosis:
• greatly increases neuronal excitability.
• Rise in arterial blood pH from 7.4 to 7.8 or 8.0 causes
cerebral epileptic seizures due to increased excitability of
some or all the cerebral neurons.
Acidosis
• greatly depresses neuronal activity; a fall in pH below 7.0
usually causes a coma.
• For instance, in very severe diabetic or uremic acidosis,
coma virtually always develops.
115. Edris A. 115
Effect of Hypoxia on Synaptic Transmission.
• Neuronal excitability is also highly dependent on an
adequate supply of oxygen.
• Cessation of oxygen for only a few seconds can
cause complete inexcitability of some neurons.
• This is observed when brain’s blood flow is
temporarily interrupted, the person becomes
unconscious within 3 to 7 seconds,.
116. Edris A. 116
Effect of Drugs on Synaptic Transmission.
• Many drugs are known to excitability of neurons, and
others are known to excitability.
• For instance, caffeine (in coffee), theophylline (in tea), and
theobromine (in cocoa), increase neuronal excitability.
• All these increase neuronal excitability, by reducing the
threshold for excitation of neurons.
117. Edris A. 117
Strychnine:
• is best known to excitability of neurons.however, it does
not reduce the threshold for excitation; but inhibits the
action of inhibitory transmitter .
– E.g. Blocks inhibitory effect of glycine in the spinal cord.
• The effect of the excitatory transmitters is overwhelming,
when neurons so excited to rapidly repetitive discharge
leading to sever tonic muscle sparm.
120. Edris A. 120
2. Electrical synapse or Gap junction
• There is direct contact between pre and postsynaptic
nerve by gap junction.
• Thus action potential passes directly from cell to
cell, through gap junction that connects the cells.
• It is two-way transmission (bidirectional) allows for
synchronization of activity,
• It is faster than chemical synapse transmission since
no synaptic delay.
• It occurs in smooth and cardiac muscle
121. Edris A. 121
• The structure of an electrical synapse
The gap junctions at electrical synapses permit
current of ions to flow passively between pre- and
postsynaptic membranes
• This current flow changes the postsynaptic
membrane potential, initiating the generation of
postsynaptic action potentials .
