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Excitable tissues nerve
1. 1
EXCITABLE TISSUES
qCells and tissues in which excitation is accompanied
by action potential, distributed along the cellular
membrane.
qThis is a property of the bodies of nerve cells and their processes—
nerve fibers, muscle fibers or cells, and some elongated plant cells
qNerves and muscles are studied together because both arc excitable
structures that conduct impulses. but the muscle contract
2. 2
NERVES
qNeurons in the mammalian central nervous system come in
many different shapes and sizes.
3. 3
NERVES
qNeurons in the mammalian central nervous system come in
many different shapes and sizes.
qPerikayon (soma) - nerve cell body, contains nucleus and typical cell
organelles. It is the metabolic center of the neuron.
a. Nucleus - large, central in most, large amount of euchromatin
(intense synthetic activity), Barr body (Dormant X chromosome of
females).
b. Rough endoplasmic reticulum (RER) - lots for synthesis of structural
and transport proteins, Nissl bodies are condensations of the RER and
free ribosomes.
c. Golgi apparatus - only found near nucleus in perikaryon. Expected,
since intense synthetic activity of neurotransmitters and/or
neurohormones.
4. 4
NERVES
qDendrite - cell process, may be branched, forms receptive area for
synaptic contacts from other neurons,
qHas tiny rough projections or spines called gemmules that may be
points of synaptic contact,
qDendrites from larger neurons may be lightly myelinated by
oligodendroglia.
qNeurons may have more than one dendrite.
qCytoplasm in these processes similar to that of perikaryon, but no
golgi bodies.
5. 5
NERVES
qAxon – a single, long, cell process extending away from perikaryon,
may be branched,
qEnds of branches form synapses with other neurons or muscle cells
qMay be myelinated by either oligodendroglia in CNS or Schwann cells
in PNS..
6. 6
NERVES
qEach neuron has only one axon..
qAxon hillock (pyramid shaped region where axon originates from the
perikaryon)
qInitial segment (unmyelinated intitial portion of axon)
qremainder of axon (may be myelinated or unmyelinated, may be
branched)
7. 7
NERVES
qAxons carry electrical impulses (action potentials) to synapses at end
of axon.
qExcept for the axon hillock and the synaptic bouton, the axon
cytoplasm (axoplasm) has few organelles, microtubules, or
microfilaments.
qNot much synthetic activity in this part of neuron. The synaptic button
granules or vesicles in which the synaptic transmitters secreted by the
nerves are stored.
qThe axon divides into presynaptic terminals, each ending in a number
of synaptic knobs which are also called terminal buttons or boutons
8. 8
NERVES
qBased on the number of processes that emanate from their cell body,
neurons can be classified as unipolar, bipolar, and multipolar
qMultipolar - more than two processes (one axon plus multiple
dendrites), most of neurons in brain and spinal cord are of this type
qBipolar - two major processes (axon and dendrite), but may be
branched at ends, sensory neurons in retina, cochlea, and olfactory
epithelium are of this type
9. 9
NERVES
q Pseudounipolar - two major processes that are fused along portions
closet to perikaryon - found in spinal ganglia and some cranial ganglia.
qUnipolar have one process, with different
segments serving as receptive surfaces and
releasing terminals.
10. 10
NEURON CLASSIFICATION BASED ON FUNCTION
q Motor neurons - efferent, action potential moves from CNS to
effector organ (e.g. muscle)
qSensory neurons - afferent, action potential moves from sensory
organ to CNS (e.g. neuron processes associated with pacinian corpuscles,
touch, pressure)
qInterneurons - form connections between neurons
11. 11
GLIAL CELLS
q There are many more glial cells in the nervous system than there are
neurons.
qThese cells are situated among the neurons and are generally smaller.
qIn sections stained with hematoxylin - eosin, only the glial cell nuclei
show up.
qSpecial staining techniques are necessary if their cell bodies are to be
easily differentiated from surrounding cells.
12. 12
GLIAL CELLS - Astrocytes
q Two types:
1. Protoplasmic astrocytes:
a. Granular cytoplasm, many branches on short processes
b. Some of processes are closely applied to neurons, while others form
intimate contacts with blood vessels.
c. Thought to form a conduit for nutrients from blood vessels to neurons.
d. Found in gray matter.
e. Protoplasmic astrocytes have a membrane potential that varies with the
external K+ concentration but do not generate propagated potentials
f. Produce substances that are tropic to neurons, and they help maintain
the appropriate concentration of ions and neurotransmitters by taking up
K+ and the neurotransmitters glutamate and γ-aminobutyrate (GABA)
13. 13
GLIAL CELLS - Astrocytes
2. Fibrous astrocytes:
a. Contain many intermediate filaments, are found primarily in white
matter
b. Function not well understood
qBoth types send processes to blood vessels, where they induce
capillaries to form the tight junctions making up the blood–brain barrier.
14. 14
GLIAL CELLS - oligodendroglia
qSmaller than astrocytes, fewer processes
qIn white matter, these cells form the myelin sheaths that are around
many axons, in gray mater they may lightly myelinate some dendrites
q Also called oligodendrocytes
qFound in both gray and white matter
qAnaologous to Schwann cells of peripheral nervous system
qThese cells must be cultured with neurons in order to get neurons to
grow in tissue culture. Suggests intimate interactive association.
15. 15
GLIAL CELLS - microglia
qElongate nucleus with mostly heterochromatin
q Small cell body that is elongated
qCan be differentiated from other glia by elongate nucleus. Other glia
have a spherical nucleus
16. 16
GLIAL CELLS - ependymal cells
qCiliary action acts to circulate cerebral spinal fluid.
q Ciliated cells forming single layer of cuboidal epithelium that lines the
entire neurocoel
qNeurocoel is the cavity of the chordate cerebrospinal system,
consisting of the ventricles of the brain and the central canal of the spinal
cord, regarded as a unit.
17. 17
PROPERTIES OF NERVES
qThis is the ability of living tissues to respond to various stimuli.
qIt is an electric phenomenon, and the electric changes that accompany
nerve excitation are called the action potential.
qSuch changes are very small and very rapid. so their magnitudes are
measured in millivolts (mV) while their durations are measured in
milliseconds (msec).
qThey are recorded by microelectrodes connected to either a
galvanometer or a cathode ray oscilloscope (CRO ).
1. Excitability
18. 18
qA stimulus is a change in the environment around the nerve (or
muscle)which may be either chemical, thermal, mechanical or electrical.
qIn laboratories, electrical stimuli are preferred because they can be
accurately controlled (both in strength and duration) and, in addition,
they leave the stimulated structures without damage.
q2 types of electric currents can be used for stimulation of excitable
tissues :
a. The galvanic current: This is a constant (or direct) current (D.C.)
which is obtained from a battery.
b. The faradic current: This is an alternating current (A.C.) like the
induction currents used in laboratories for nerve stimulation.
The stimulus
19. 19
qThe physicochemical change produced by various stimuli in the nerve
is called the nerve impulse.
qSuch impulse is actively conducted along the nerve fibre and it can be
conducted in both directions.
qIn the body, each nerve conducts impulses in one direction only (motor
nerves toward the effector organs and sensory nerves toward the nervous'
system).
2. Conductivity
qConduction in the normal direction is called orthodromic conduction,
qIf it occurs in the opposite direction due to any cause, it will be called
antidromic cmuluction
Does antidromic conduction occur in the brain under normal conditions?
20. 20
qStates that "A threshold (minimal) stimulus produces a maximal
response " i.e. a maximal action potential in nerve and muscle fibres and
a maximal contraction in muscle fibres.
qTherefore as long as other factors that affect excitability remain
constant:
qIncreasing the intensity of the stimulus above the threshold value
produces no further increase in the action potential or muscle contraction
(3) All or none law (or rule)
21. 21
qThe all or none law is obeyed in the following structures:
a. A single nerve fibre
- A motor unit is made up of a motor neuron and the skeletal muscle fibers innervated
by that motor neuron's axonal terminals.
(3) All or none law (or rule)
c. The cardiac muscle and some smooth muscles which act as one unit
called syncytium
b. A single skeletal muscle fibre and the motor unit
- Groups of motor units often work together to coordinate the contractions of a single
muscle; all of the motor units within a muscle are considered a motor pool.
22. 22
qHowever, nerve trunks and whole skeletal muscles (which contain
many fibres) do not obey the law.
(3) All or none law (or rule)
Why?
The threshold intensity for stimulation varies in the different types of
nerve and muscle fibres (i.e. it is not equal).
Therefore if the intensity of stimulation is increased in these structures,
the response will also increase till reaching a maximum.
23. 23
qThe nerve fibre adapts to stimulation by a constant current so no
response occurs during passage of the current.
(4) Accommodation (or adaptation)
(5) Infatiguability
qNerve fibres are not fatigued by continuous stimulation
24. 24
1. Intensity (strength) of the stimulus: Sub-threshold stimuli produce only
local responses that don't initiate action potentials .
Factors that determine the effectiveness of stimuli
If the intensity is increased slowly the nerve will not respond because of
the property of accommodation
2. Rate of increase in the intensity of stimuli; Sub-threshold stimuli
that are gradually increased produce a response only with a rapid
increase in the intensity of stimuli
25. 25
3. Duration of stimulus (duration of current): The relation between the
intensity of a stimulating current and the duration (time) of its flow
necessary to set up an impulse is shown in the strength-duration curve
Factors that determine the effectiveness of stimuli
26. 26
qWithin limits, there is a reciprocal relationship between the current
strength and duration of flow required to produce an impulse
qThere is a minimal duration needed for excitation below which no
excitation occurs whatever be the strength of the stimulus.
qRHEOBASE: This is the minimal strength (or threshold intensity ) of a
galvanic current that can set up an impulse.
qCHRONAXIE: This is the duration of current flow required for
excitation when using a strength equal to twice (or double) the rheobase.
qThe time required for excitation when using the rheobase is called the
utilization time
27. 27
qWhat is the significance of the Chronaxie?
qIts measurement can be used to compare the excitability of
different tissues, or that of the same tissue under different conditions.
qThe chronaxie is a good index for the degree of excitability (the shorter
the chronaxie the greater the excitability versa).
In the strength-duration curve to
the right, which nerve is more
excitable?
28. 28
qThe curve for the slower fibres would be shifted to the right, indicating
that for a given stimulus strength, a longer stimulus duration would be
needed to bring the slower fibres to threshold.
Q How would the strength-duration curve for a set of slow fibres (not
very excitable) compare to the strength-duration curve for a set of quick
fibres (very excitable)?
29. 29
RESTING MEMBRANE POTENTIAL REVIEW
qOutside the cell membranes there are mainly Na+, Cl- and HCO3 while
inside the cell there are mainly K+ and organic protein anions
qIn neurons the potential difference about -70 mV
qRM P is due to an unequal distribution of ions on both sides of the
membrane with relatively excess cations outside and excess anions inside
qThis is produced as a result or 2 main factors (a) Selective
permeability of cell membranes (b) The N a+/K+ ATPase
30. 30
RESTING MEMBRANE POTENTIAL REVIEW
(a) The electrical gradient is directed inwards
qK+ ions tend to diffuse outside the cells. However, this is limited
because:
(b) The +ve charge on the outside of the membranes repels K+ ions
inwards.
(c) The sodium-potassium pump actively drives K+ ions inwards
qThe concentration gradient for Cl- and HCO3 is directed inwards, so
these anions tend to diffuse into the cells.
qThis is limited because the interior of the cells has a great -ve charge,
and accordingly, they are expelled out of the cell along this electrical
gradient
31. 31
CHANGES THAT ACCOMPANY PROPAGATION OF A NERVE
IMPULSE
The Action Potential (AP)
(1) ELECTRIC CHANGES
qThis refers to the changes in potential that occur in excitable tissues
when stimulated
qIt is transmitted as a self-propagated disturbance called impulse
qStimulating the nerve (by an electric stimulator) is marked by a
stimulus artifact, which is due to current leakage from the stimulating
electrode to the recording (external) electrode.
qLatent period (which is an isopotcntial interval representing the time
taken by the impulse to reach the recording electrode) after which the AP
is recorded.
33. 33
qThe AP consists of 2 main stages (called depolarization and
repolarization)
q This is followed by 2 other stages known as after-
depolarization and after-hyperpolarization.
34. 34
qDepolarization (DP)
qThis is loss of the normal resting polarized state of the
membrane
qIt is recorded as a rise of the membrane potential in the
positive direction from -70 mV towards the isopotential line
(zero potential)
qIt produces the ascending limb of the A.P
qDP develops slowly. but after an initial 15 mV of DP (i.e.
MP becomes about -55 mV). the rate of DP suddenly increases
(so this point is called the firing level)
35. 35
qDepolarization (DP)
qDP then proceeds rapidly till the resting membrane potential
is lost
qThe potential difference between both sides of the
membrane becomes zero
qthis change is called overshoot or reversal of polarity, and it
results in an A.P. having a magnitude of 105 mV (from -70 to
+35 mV)
qThe membrane potential the reaches +35m V (indicating
that the inner surface of the membrane becomes positive
relative to the outer surface.
36. 36
qRepolarization (RP)
qThis is restoration or the normal resting polarized state of
the membrane
qIt is recorded as a fall of the membrane potential in the
negative direction from +35 mV to -70 mV.
qRP proceeds immediately and rapidly after the overshoot is
reached
q It produces the descending limb of the A.P.
qWhen RP is 70-80% completed, its rate decreases for about
4 msec. This stage is called after-depolarization (or negative
after-potential)
37. 37
qRepolarization (RP)
qAfter RP is completed the membrane potential overshoots to
the negative side (by about 1-2 mV) leading to
hyperpolarization of the membrane
qThis stagc is called after-hyperpolarization (or positive
after-potential).
qIt lasts about 40 msec but its magnitude gradually declines
till the normal resting membrane potential is restored
38. 38
Ionic basis (or mechanisms) of DP and RP
qThe initial slow DP is produced by the stimulating current
itself . How?
qStimulating current arc cathodic in nature, which adds
negative charges outside the nerve membrane
qThus the potential difference between both sides of the
membrane is decreased
qThe membrane potential becomes less -vc than at the resting
state. This is called electrotonic DP.
Depolarization
39. 39
qThe rapid phase of DP and the overshoot are produced by an
increase in Na+ influx (= entrance) into the nerve fiber as a
result of increased Na+ conductance of the nerve membrane
qIncreased permeability occurs secondary to marked increase
in the Na+ permeability of the membrane through opening of
specific Na+ channels in the membrane.
qEach Na+ channel has an activation gate at the outer surface
of the membrane and an inactivation gate at its inner surface.
qThe membrane Na+ conductance (and consequently the Na
influx ) is increased only when both gates are opened.
40. 40
qIn the resting state, only the inactivation gates are open so
the membrane permeability to Na+ is low
qWhen the nerve is stimulated the Na+ activation gates also
open thus the membrane permeability and conductance to Na+
as well as Na+ influx are markedly increased
qOpening of the Na+ activation gates is voltage-dependent.
qThey start to open when the initial electrotonic DP becomes
7 mV
qThis allows Na influx. which further decreases the
membrane polarity leading to opening of more gates.
41. 41
qThis results in more Na+ influx and more decrease of the
membrane polarity, which leads to opening of more and more
gates and more Na+ influx.
qSuch process continues in the form of a vicious circle
(i.e. by a positive feedback mechanism ) till all gates open
qThe rate of opening of the Na+ activation gates is slow
between 7 and I5 mV of DP (i.e. till a membrane potential of
about -55 mV) leading to slow DP.
qAfter15 mV of DP, the rate of opening of these gates
suddenly increases leading to much acceleration of DP (the
firing level)
42. 42
(a) Closure of the Na+ inactivation gates
(b) Reversal ofthe direction of eleclrical gradient for Na+
(2) K+ efflux (exit) from the nerve fibre:
Repolarization (RP) and after-potentials
RP of the membrane takes place rapidly after DP as a result of:
(1) Stoppage of Na+ influx due to:
qThis occurs through specific K+ channels that contain a
single gate located toward the inside of the membrane.
qThe decrease in membrane polarity during DP leads to
opening of the K+ gates, thus the K+ conductance is markedly
increased and K+ ef1ux occurs.
43. 43
qThe negative after-potential stage is clue to slowing of the
rate of K+ efflux.
qThe positive after-potential stage is due to slow return of the
K+ channels to the closed state (which allows prolonged K+
efflux)
qThe process is however slower than opening of the Na+
channels so the increase in K+ conductance is slightly delayed
qThe slow opening and delayed closure of the K+ channels
may explain the phenomenon of accommodation that occurs in
nerves
qFollowing the AP, the resting Na+ and K+ ionic gradients is
restored by the action of the Na+/K+ pump.
44. 44
qNormally, both the concentration and electrical gradients for
Ca2+are directed inwards
qThe Ca2+ conductance increases during nerve excitation
leading to Ca2+ influx.
Role of Ca2+ in Nerve excitation
qCa2+ contributes to DP (and in some invertebrates. it is
primarily responsible for the AP)
qCa2+ influx occurs via voltage-gated Ca2+ channels which
are also slightly permeable to Na+ (so they arc called Ca2+-
Na+ channels)
45. 45
qThey are however very slow to become activated, so they
are also called slow channels (in contrast to the voltage-gated
Na+ channels which arc called fast channels)
Role of Ca2+ in Nerve excitation
qThe extracellular Ca2+ concentration also affects nerve
excitability
qIts decrease increases the excitability while its increase
decreases the excitability and stabilizes the nerve membrane
46. 46
qETPs are localized potential changes that occur in nerves
when stimulated by sub-threshold constant currents
Electrotonic potentials (ETPs) and the local response
qThere are 2 types of the ETPs both of which are passive
changes in the membrane polarization
qThis is produced by addition of subtraction of charges
through the stimulating current) that decay (i.e. disappear)
gradually
47. 47
qThis is the potential change that occurs when using anodal
(+ve) currents for stimulation
(A) Anelectrotonic potential (or anelectrotonus)
qIt is a state of hyperpolarization caused by addition of +ve
charges at the outer surface of the nerve membrane.
qThe magnitude of the potential change is proportionate to
the strength of the stimulus
qIt is associated with a decrease of excitability of the nerve
and with strong anodal currents, the nerve excitability may be
completely lost ( anodal block)
qIt takes the membrane potential away from firing level
(which inhibits discharge of impulses).
48. 48
qThis is the potential change that occurs when using cathodal
(-ve) currents for stimulation
(A) Catelectrotonic potential (or catelectrotonus)
qIt is a state of partial DP caused by addition of –ve charges
at the outer surface of the nerve membrane.
qThe magnitude of the potential change varies with the
strength of the stimulating current
qIt is associated with an increase of excitability of the nerve,
50. 50
(A) In unmyelinated nerve fibres
qNerve impulses are propagated along unmyelinated nerve
fibres in the form of a wave of APs
qLocal circular currents flow between the activated point and
the neighbouring inactive areas of the nerve membrane
qThe initial stimulus causes reversal of polarity and an AP at
the point of stimulation
q+ve charges from the inactive areas flow into the initial area
of negativity produced by the AP (= area of current sink )
51. 51
qThis decreases the polarity at the inactive areas (
electrotonic depolarization) which produces an AP initiating
on reaching the firing level.
qThe latter areas, in turn, electrotonically depolarize the
membrane in front of it through local circular currents and this
sequence of events moves regularly along the nerve fibre to its
end.
qthe nerve impulse is self-propagated and once it leaves a
point this point will soon repolarize
qthus a repolarization wave starts after the depolarization
wave and is propagated in the same direction
52. 52
(B) In myelinated nerve fibres
qNerve impulses are propagated along myelinated nerve
fibres by a mechanism called the saltatory conduction
qMyelin surrounds the nerve axon and is interrupted at
regular intervals at the nodes of Ranvier
qIt is an insulator to current flow (in contrast to the nodes of
Ranvier which easily permit current flow because of their high
permeability to Na)
qCircular currents also flow in myelinated nerve fibres but
the +ve charges jump from the inactive nodes to the area of
current sink at the active node
53. 53
qThis leads to electrotonic depolarization and production of
an AP at the inactive nodes, which in turn activates the
neighbouring nodes.
qThis jumping of DP from node to node is called saltatory
conduction and it results in:
(a) Increasing velocity of conduction
(b) Conservation of energy (because excitation occurs only in
the nodes and not allover the nerve membrane)
54. 54
(2) EXCITABILITY CHANGES
qDuring propagation of a nerve impulse (i.e. during an AP).
The excitability of nerve fibres passes in the following phases
(a) Absolute refractory period (ARP):
§During this period, the nerve is completely inexcitable.
§No stimulus can excite it whatever its strength
§It corresponds to the ascending limb of the AP from the time
the firing level is reached
§That is during DP and overshoot and upper part of the
descending limb (until RP is about 1/3 complete)
55. 55
(b) Relative refractory period (RRP):
§During this period, nerve excitability is partiality recovered
§Stronger stimuli than normal are required for excitation
§It corresponds to the remaining part of the descending limb
of the AP till the start of after-depolarization
§That is during the later 2/3 of RP
56. 56
(c) Supernormal phase (or period):
§During this period nerve excitability is increased.
§Weaker stimuli than normal can excite the nerve
§It corresponds to the period of after-depolarization
57. 57
(d) Subrnormal phase (or period):
§During this period nerve excitability is decreased.
§Stronger stimuli than normal are required for excitation
§It corresponds to the period of afler-hyperpolarization.
59. 59
Factors that affect nerve excitability
(1) Temperature: Cooling decreases nerve excitability while
warming increases it
(2) Pressure: Mechanical pressure on a nerve reduces its
excitability.
(3) Blood supply: Nerve excitability is decreased in cases of
ischemia.
(4) Oxygen supply: O2 lack decreases nerve excitability.
(5) H+ concentration: Alkalinity increases while acidity
decreases excitability of nerves.
60. 60
(6) Chemicals: Nerve excitability is decreased by excess CO2
and alcohol as well as by anesthetic drugs e.g. ether,
chloroform and cocaine.
(8) Electrolytes: The concentrations of Na+ K+ and Ca2+ in
the extracellular fluid affect nerve excitability as follows
61. 61
Ionic changes that increase nerve excitability
1- Decreased Ca2+ concentration: This increases the
membrane permeability to Na+ and decreases the amount of
DP necessary to initiate the changes in Na+ and K+
conductances that produce the AP.
2- Increased Na concentration: This facilitates the process of
DP
3- Increased K+ concentration: This favours K influx which
leads to DP thus the nerve excitability will increase
62. 62
Ionic changes that decrease nerve excitability
1- Increased Ca2+ concentration : This decreases the
membrane permeability to Na+ and increases the amount of
DP necessary to initiate the changes in Na+ and K+
conductances that produce the AP
2-Decreased Na concentration : This decreases nerve
excitability by delaying the process of DP
3- Decreased K+ concentration : This favours K+ efflux
which leads to hyperpolarization, thus the nerve excitability
will decrease
63. 63
Methods of producing nerve block
qPropagation of impulses by nerves can be blocked (i.e.
prevented) by one of the following methods :
(1) Physical methods e.g. application of cold or a strong
anelectrotonus
(2) Mechanical methods (e.g. application of pressure on the
nerve).
(3) Chemical methods: These include:
(a) The ionic changes that decrease nerve excitability i.e.
increased Ca2+ and decreased Na+ or K+ concentration in the
extracellular fluid
64. 64
q(b) Use of certain chemical substances known as the
membrane stabilizers which include mainly the local
anesthetic drugs (e.g. cocaine and novocaine)
§These drugs markedly decrease the membrane
permeability to Na+ (by preventing opening of the Na+
channel activation gales)
§So the depolarization process is inhibited and nerve
impulses fail to be produced
65. 65
(3) METABOLIC CHANGES
qThe metabolic processes that occur in nerves are generally
similar to those occurring in muscles (O2 and ATP)
qIn resting nerves, they occur at a low rate (mainly to
maintain the polarized state) but they are much increased
during transmission of nerve impulses
qThe breakdown of ATP supplies the energy required for the
sodium potassium pump and nerve impulse propagation
qIt is resynthesized by energy derived from breakdown of
glycogen.
qNerve fibres are also rich in vitamin B1 which is necessary
for their metabolic activities
66. 66
(4) THERMAL CHANGES
qResting nerves liberate little heat as a result of their low
metabolic rate.
qDuring nerve impulse transmission the heat production by
nerves is markedly increased, and is liberated in the following
2 stages :
(1) Initial heat: This coincides with propagation of spike (i.e.
during ionic migration), and it is due to anaerobic breakdown
of ATP
(2) Recovery (delayed) heat: This follows propagation of the
spike, and it is due to aerobic reactions that liberate the energy
required for ATP resynthesis.
67. 67
Types of mammalian nerve fibres
The mammalian nerve fibres are classified according to their
diameters into the following types:
( 1) Group A nerve fibres :
§These have the largest diameters (3-20 microns)
§The have highest speeds of conduction ( 15-120 m/sec)
§They are further subdivided into alpha, beta, gamma & delta
nerve fibres
§ E.g. the somatic nerve fibres that transmit motor impulses &
deep sensations
§They are most sensitive to pressure (i.e. the conduction of
impulses in these nerves can be readily blocked by pressure)
68. 68
( 2) Group B nerve fibres :
§These have the smaller diameters (1.3 - 3 microns)
§They have moderate speeds of conduction (3-15 m/sec)
§E.g. the myelinated preganglionic autonomic nerves
§They arc most sensitive to O2 lack
69. 69
( 3) Group C nerve fibres :
§These have the smallest diameters (0.3-1.3 microns)
§The have slowest speeds of conduction (0.5-3 m/sec)
§E.g. the unmyelinated postganglionic autonomic nerves
§They arc most sensitive to local anaesthetics
71. 71
qThe area of contact between a nerve fibre and a muscle fibre
is called the motor end plate (M.E.P. ) or neuromuscular
junction
qAs the nerve approaches the muscle, it loses its myelin
sheath and its axon is branched.
qThe tip of each branch (sole foot ) is covered by the
neurolemma which continues with the sarcolemma ((the outer
membrane of the n1uscle fibre)
qEach sole foot lies in a depression in the plasma membrane
(the inner membrane of the muscle fibre) called the synaptic
gutter
73. 73
qWhere the membrane is thrown into many folds called the
palisades
qThere is no protoplasmic continuity between the nerve and
muscle fibres.
qThey are separated by the synaptic cleft in which the
chemical transmitter acetylcholine is released from the
vesicles present in the sole feet.
qThe sarcoplasm at the motor end plate is granular and
contains the cholinesterase enzyme which hydrolyzes
acetylcholine.
74. 74
Miniature end plate potential ( M. E.P.P.)
qThis is a state of persistent localized subthreshold DP (0.5
mV in amplitude) of the muscle fibres at the M.E.P. during
rest.
qIt does not reach the firing level (so it does not lead to an
AP)
q It is due to continuous release of small amounts of
acetylcholine
qArising from the continuous rupture of a few vesicles that
contain this chemical transmitter at the nerve terminals
75. 75
Mechanism of neuromuscular transmission
qWhen a motor nerve is stimulated, the generated impulse is
propagated toward the M.E.P
qit causes movement of'Ca2+ from the extracellular fluid into
the nerve terminals
q Ca2+ cause rupture of acetylcholine vesicles leading to
release (exocytosis) of this transmitter into the synaptic cleft
qAcetylcholine then combines with nicotinic receptors in the
muscle membrane
76. 76
qThis increases its permeability to Na+ through opening of
ligand-gated Na+ channel.
qNa+ influx increases resulting in DP of the muscle at the
M.E.P.. which is called the end plate potential
qThis normally reaches the firing level which starts an A P
along the surface of the muscle
qThe released acetylcholine is rapidly hydrolyzed by the
cholinesterase enzyme so that the re-excitation of the muscle
wouldn’t occur.
78. 78
Properties of neuromuscular transmission
1. At the M.E.P. impulses are conducted in one direction only
2. Transmission of impulses at the M. E.P. is delayed 0.5- 0. 7
millisecond due to the time required for:
(a) Release of acetylcholine
(b) Passage of acetylcholine across the synaptic cleft and its
combination with the nicotinic receptors in the muscle
(c) Increase in the permeability of the muscle membrane to Na
(d) Increase in Na+ influx till the firing level
3. Transmission of impulses at the M.E.P. readily fatigues after
repeated stimulations (mostly due to exhaustion of Ach)
4. Transmission of impulses at the M.E.P. is readily affected
by drugs
79. 79
Drugs that affect neuromuscular transmission
(A) Drugs that block neuromuscular transmission
1. Curare (tubocurarine) competitively inhibits Ach interaction
at the Nm receptors. α- neurotoxins (α- bungarotoxin, α-
cobrotoxins) irreversibly blocks.
2. Botulinum toxin: From Clostridium botulinum. The toxin
inhibits the release of ACh
80. 80
(B) Drugs that stimulate neuromuscular transmission
1. Acetylcholine-like drugs that are not rapidly hydrolyzed by
the cholinesterase enzyme and act mainly at the M. E.P. e.g.
carbacol.
2. Drugs that preserve the liberated acetylcholine at the M.E.P.
by antagonizing the cholinesterase enzyme e.g. prostigmine
and eserine
