Chapter 22
- Neuromuscular Physiology and Pharmacology
- J. A. Jeevendra Martyn
The physiology of neuromuscular transmission could be analyzed
and understood at the most simple level by using the classic model of nerve signaling
to muscle through the acetylcholine receptor. The mammalian neuromuscular junction
is the prototypical and most extensively studied synapse. Research has provided
more detailed information on the processes that, within the classic scheme, can modify
neurotransmission and response to drugs. One example of this is the role of qualitative
or quantitative changes in acetylcholine receptors modifying neurotransmission and
response to drugs.[1]
[2]
In myasthenia gravis, for example, the decrease in acetylcholine receptors results
in decreased efficiency of neurotransmission (and therefore muscle weakness)[3]
and altered sensitivity to neuromuscular relaxants.[1]
[2]
Another example is the importance of nerve-related
(prejunctional) changes that alter neurotransmission and response to drugs.[1]
[4]
At still another level is the evidence that
muscle relaxants act in ways that are not encompassed by the classic scheme of unitary
site of action. The observation that muscle relaxants can have prejunctional effects
[5]
or that some nondepolarizers can also have agonist-like
stimulatory actions on the receptor[6]
while others
have effects not explainable by purely postsynaptic events[7]
has provided new insights into some previously unexplained observations. Although
this multifaceted action-response scheme makes the physiology and pharmacology of
neurotransmission more complex, these added insights also bring experimentally derived
knowledge much closer to clinical observations.
Crucial to the seminal concepts that have developed relative to
the neurotransmitter acetylcholine and its receptor systems has been the introduction
of powerful and contemporary techniques in molecular biology, immunology, and electrophysiology,
as well as more elegant techniques for observations of neuromuscular
junction in vivo.[8]
These have augmented the more
traditional pharmacologic, protein chemical, morphologic, and cytologic approaches.
[9]
Research has elucidated the manner in which
the nerve ending regulates the synthesis and release of transmitter and the release
of trophic factors, both of which control muscle function, and how these processes
are influenced by exogenous and endogenous substances.[8]
[9]
[10]
[11]
Research continues into how receptors are synthesized and anchored at the end plate,
the role of the nerve terminal in the maturation process, and the synthesis and control
of acetylcholinesterase, the enzyme that breaks down acetylcholine. Several reviews
that provide detailed insights into these areas are available.[8]
[9]
[10]
[11]
[12]
[13]
