In this article we will discuss about the meaning and blocking of neuromuscular transmission.
Meaning of Neuromuscular Transmission:
It is the process by which the nerve action potential is converted into a muscle action potential.
Events involved in the neuromuscular transmission are:
i. Action potential reaching the motor neuron terminal.
ii. Depolarization of motor neuron terminal.
iii. Calcium ion influx into the terminals of the neuron.
iv. Synaptic vesicles binding to the pre-junctional membrane.
v. Release of neurotransmitter (acetylcholine—ACh) by exocytosis.
vi. Diffusion of ACh through the synaptic clefts.
vii. Binding of ACh to the receptors present on the post-junctional membrane.
viii. Opening of ligand-gated sodium channels at the end plate region of the post-junctional membrane.
ix. Slow influx of sodium ions.
x. Development of end plate potential.
xi. When end plate potential reaches sufficient value (firing level), there will be opening of the voltage- gated sodium channels at the extra-junctional region of the muscle.
xii. Sudden rush of sodium ions from ECF into ICF.
xiii. Development of action potential in the muscle fiber.
xiv. Removal of ACh by diffusion and degradation by cholinesterase enzyme present on the post-junctional membrane.
For all practical purposes, end plate potential is also a local potential and hence it has all the characteristic features of local potential. Even at rest, there will be very small amount of release of ACh at NMJ and this brings about the development of minute amount of potentials namely miniature end plate potentials. Since they will be very weak, they die off without producing any effect.
The structural difference between neuromuscular junction and synapse is, at synapses the post-junctional region is contributed by part of some other neuron and not by muscle.
Blocking of Neuromuscular Transmission:
Blocking of neuromuscular transmission can be done by different ways. Some of the substances used to block the transmission by acting at the pre-junctional region and some at the post-junctional region. Blocking the transmission leads relaxation of the muscle.
Pre-junctional blockers:
Botulinum toxin (from Clostridium botulinum) prevents the synthesis and release of ACh.
Clinically, the neuromuscular blockers are used extensively. The mechanism of action of the different blockers varies.
1. Competitive inhibitors (e.g. tubocurarine):
They bind to the receptors available on the post-junctional membrane. Hence these receptors will not be available for ACh to bind when ACh gets liberated from the prejunctional regions.
Because of this, there will not be opening of ligand-gated sodium channels and hence no development of end plate potential. Consequently, muscle action potential cannot get developed. Unlike ACh, which gets metabolized fast, curare group of drugs metabolism is slow, and hence action continues for prolonged duration.
2. Depolarizing blockers: (e.g. succinylcholine):
They also bind to the ACh receptors present on the post-junctional membrane and bring about the depolarization of the post-junctional membrane much like ACh. However, since the metabolism of this substance cannot be brought about by cholin- esterase, there will be a persistent end plate potential at the post-junctional membrane. Because of this, the post-junctional membrane cannot get stimulated again.
3. Anticholinesterases (e.g. neostigmine, physostigmine, nerve gas (di-isopropyl fluorophosphate):
All these substances antagonize/inactivate the enzyme cholinesterase. Hence ACh cannot get metabolized. This will also bring about the persistent depolarization of the post-junctional membrane. When the muscle is not in the resting state, the production of action potential cannot occur. And hence block the transmission.
Muscle relaxants are used:
1. During surgeries.
2. During electroconvulsive therapy.