Page 314 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Disorders of Neuromuscular Transmission
Neuromuscular transmission is a sequence of cause high concentrations of ACh, as of succi-
events (→ A) that can be interrupted at various nylcholine, cause continuous depolarization
levels. The action potential is carried along by of the subsynaptic membrane and so inacti-
+
+
activation of the Na channels to the nerve vate the postsynaptic Na channels. The re-up-
ending, where it depolarizes the cell mem- take of choline into the nerve ending can be in-
2+
Systems brane and thus opens the voltage-gated Ca hibited by Mg and hemicholine.
2+
2+
The most important disease affecting the
ions that enter the nerve
channels. The Ca
end-plates is myasthenia gravis, a muscle pa-
ending mediate the fusion of acetylcholine
ralysis that results from blockage of neuro-
(ACh)-containing vesicles with the presynap-
Neuromuscular and Sensory into the synaptic cleft. ACh binds to receptors antibodies against the ACh receptors in the
tic membrane, whereupon ACh is released
muscular transmission (→ B). It is caused by
subsynaptic membrane which accelerate the
of the subsynaptic membrane and in this way
opens nonspecific cation channels. The depolar-
breakdown of the receptors (→ B1). This auto-
ization of the subsynaptic membrane is trans-
immune disease can be caused by infection
mitted to the postsynaptic membrane where,
with viruses that have an ACh-receptor-like
+
through opening of voltage-gated Na chan-
structure. Myasthenia may also occur in
patients with a benign tumor of the thymus.
nels, an action potential is initiated that rapidly
those who express special subtypes (DR3 and
ACh is broken down by acetylcholinesterase;
DQw2) of the major histocompatibility com-
the choline which has been split off is again
10 spreads over the entire muscle membrane. The formation of such antibodies is favored in
taken up into the nerve ending and used again
plex (MHC class II). In patients with myasthe-
for the synthesis of ACh. nia gravis, repetitive stimulation of a motor
Abnormalities can affect any element of this nerve will at first cause the production of a
process. Local anesthetics, for example, inhibit normal summated muscle action potential
the voltage-gated Na + channels of the neuron whose amplitude will, however, decrease
and thus interrupt nerve transmission to the through progressively increasing “fatigue” of
end-plate. The Ca 2+ channels can be blocked neuromuscular transmission (→ B2).
by antibodies (see below). Botulinus toxin inac- Another autoimmune disease that impairs
tivates synaptobrevin, the protein responsible neuromuscular transmission is the pseudo-
for binding the ACh-containing vesicles to the myasthenic syndrome of Lambert and Eaton
plasma membrane and thus for the release of (→ C). This condition often arises in patients
ACh. The ACh receptors can also, like the Ca 2+ affected by a small-cell carcinoma of the lung.
channels, be blocked by antibodies which fur- Ca 2+ channels in the plasma membrane of the
thermore accelerate the internalization and tumor cells sensitize the immune system and
breakdown of the receptors. The receptors can stimulate the formation of antibodies that
also be blocked by curare that, without itself also react with the Ca 2+ channels of the end-
having an effect, competitively inhibits the plate (→ C1). Due to inhibition of the Ca 2+
binding of ACh to the receptors. channels, the summated muscle action poten-
Succinylcholine (suxamethonium chloride) tial is at first small, but is progressively nor-
leads to continuous stimulation of the recep- malized, because with the repetitive stimula-
tors, continuous depolarization of the post- tion increasing amounts of Ca 2+ are accumu-
synaptic membrane, and thus to an inactiva- lated in the nerve endings (→ C2).
+
tion of the postsynaptic Na channels. In this
way it can, like curare, block neuromuscular
transmission. In low concentrations, sub-
stances that inhibit acetylcholinesterase (e.g.,
physostigmine) increase neuromuscular trans-
mission by increasing the availability of ACh
304 in the synaptic cleft. In high doses, however,
they inhibit neuromuscular transmission be-
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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