Page 69 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

Motor End-plate “force” (= E m –E Na,K; ! p. 32 ff.) becomes
smaller when E m is less negative.
The transmission of stimuli from a motor axon +
to a skeletal muscle fiber occurs at the motor E Na,K is the common equilibrium potential for Na and
+
K and amounts to approx. 0 mV. It is also called the
end-plate, MEP (! A), a type of chemical syn-
reversal potential because the direction of I EP (= I Na
apse (! p. 50ff.). The transmitter involved is + I K), which enters the cell when E m is negative (Na +
acetylcholine (ACh, ! cf. p. 82), which binds to influx " K outflow), reverses when E m is positive (K +
+
+
the N(nicotinergic)-cholinoceptors of the sub- outflow " Na influx). As a result,
I EP # n ! p o ! γ ! (E m – E Na, K) [A]
[2.1]
synaptic muscle membrane (! A3). N-cholino- Because neurally induced EPPs in skeletal
Nerve and Muscle, Physical Work 1γ, 1δ), each of which contains 4 membrane- 70 mV) than neuronal EPSPs (only a few mV;
ceptors are ionotropic, that is, they also func-
tion as ion channels (! A4). The N-cholinocep-
muscle are much larger (depolarization by ca.
tor of the MEP (type N M) has 5 subunits (2α, 1",
! p. 50 ff.), single motor axon action potentials
spanning α-helices (! p. 14).
are above threshold. The EPP is transmitted
The channel opens briefly (! B1) (for ap-
electrotonically to the adjacent sarcolemma,
prox. 1 ms) when an ACh molecule binds to the
where muscle action potentials are generated
two α-subunits of an N-cholinoceptor (! A4).
by means of voltage-gated Na channels, re-
+
Unlike voltage-gated Na -channels, the open-
+
sulting in muscle contraction.
probability p o of the N M-cholinoceptor is not
Termination of synaptic transmission in
by the ACh concentration in the synaptic cleft
the synaptic cleft by acetylcholinesterase local-
(! p. 50 ff.).
ized at the subsynaptic basal membrane, and
2 increased by depolarization, but is determined + MEPs occurs (1) by rapid degradation of ACh in
The channel is specific to cations such as Na ,
(2) by diffusion of ACh out of the synaptic cleft
+
2+
K , and Ca . Opening of the channel at a rest- (! p. 82).
ing potential of ca. !90 mV leads mainly to an A motor end-plate can be blocked by certain
+
influx of Na ions (and a much lower outflow of poisons and drugs, resulting in muscular
+
K ; ! pp. 32 ff. and 44). Depolarization of the weakness and, in some cases, paralysis.
subsynaptic membrane therefore occurs: end- Botulinum neurotoxin, for example, inhibits the
plate potential (EPP). Single-channel currents discharge of neurotransmitters from the ves-
of 2.7 pA (! B1) are summated to yield a min- icles, and α-bungarotoxin in cobra venom
iature end-plate current of a few nA when blocks the opening of ion channels. Curare-like
spontaneous exocytosis occurs and a vesicle substances such as (+)-tubocurarine are used
releases a quantum of ACh activating thou- as muscle relaxants in surgical operations.
sands of N M-cholinoceptors (! B2). Still, this is They displace ACh from its binding site (com-
not enough for generation of a postsynaptic ac- petitive inhibition) but do not have a depolariz-
tion potential unless an action potential trans- ing effect of their own. Their inhibitory effect
mitted by the motor neuron triggers exocyto- can be reversed by cholinesterase inhibitors
sis of around a hundred vesicles. This opens such as neostigmine (decurarinization). These
around 200,000 channels at the same time, agents increase the concentration of ACh in the
yielding a neurally induced end-plate current synaptic cleft, thereby displacing curare. Entry
(I EP) of ca. 400 nA (! B3). End-plate current, I EP, of anticholinesterase agents into intact syn-
is therefore dependent on: apses leads to an increase in the ACh concen-
! the number of open channels, which is tration and, thus, to paralysis due to permanent
equal to the total number of channels (n) times depolarization. ACh-like substances such as
the open-probability (p o), where p o is deter- suxamethonium have a similar depolarizing
mined by the concentration of ACh in the syn- effect, but decay more slowly than ACh. In this
aptic cleft (up to 1 mmol/L); case, paralysis occurs because permanent
! the single-channel conductance γ (ca. depolarization also permanently inactivates
30 pS); Na channels near the motor end-plate on the
+
! and, to a slight extent, the membrane sarcolemma (! p. 46).
56 potential, E m, since the electrical driving
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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