NEUROMUSCULAR TRANSMISSION

Overview

Neuromuscular transmission occurs by a fairly simple and straightforward mechanism. The nerve synthesizes acetylcholine and stores it in small, uniformly sized packages called vesicles. Stimulation of the nerve causes these vesicles to migrate to the surface of the nerve, rupture, and discharge acetylcholine into the cleft separating nerve from muscle. Acetylcholine receptors in the end plate of the muscle respond by opening its channels for influx of sodium ions into the muscle to depolarize the muscle. The end-plate potential created is continued along the muscle membrane by the opening of the sodium channels present throughout the muscle membrane, initiating a contraction.^[13] The acetylcholine immediately detaches from the receptor and is destroyed by acetylcholinesterase enzyme, which also is in the cleft. Drugs, notably depolarizing relaxants or carbachol (a synthetic analog of acetylcholine not destroyed by acetylcholinesterase), can also act on these receptors to mimic the effect of acetylcholine and cause depolarization of the end plate. These drugs are therefore called agonists of the receptor, because to a greater or lesser extent, at least initially, they stimulate the receptor. Nondepolarizing relaxants also act on the receptors, but they prevent acetylcholine from binding to the receptor and so prevent depolarization by agonists. Because these nondepolarizers prevent the action of agonists (e.g., acetylcholine, carbachol, succinylcholine), they are referred to as antagonists of the acetylcholine receptor. Other compounds, frequently called reversal agents or antagonists of neuromuscular paralysis (e.g., neostigmine), inhibit acetylcholinesterase enzyme and therefore impair the hydrolysis of acetylcholine. The increased accumulation of undegraded acetylcholine can effectively compete with nondepolarizing relaxants, displacing the latter from the receptor (i.e., law of mass action), antagonizing the effects of nondepolarizers.