Physiologie de la jonction neuromusculaire et mécanisme d'action des curares

The physiological mediator of the neuromuscular junction is acetylcholine, synthesized by choline acetyltransferase, and hydrolyzed by cholinesterase. Acetylcholine released by nerve impulses binds to postsynaptic nicotinic receptor, opening this receptor-channel and then depolarizes the sarcolemma, generating the muscle action potential, which opens voltage-gated calcium channels. The increase in cytosolic calcium triggers muscle contraction. Presynaptic receptors to acetylcholine and various proteins of the vesicles play an important role in regulating its release. Denervation leads to upregulation of receptors. The receptor occupancy by neuromuscular blocking agents inhibits neuromuscular transmission. Succinylcholine, a depolarizing myorelaxant, is an agonist of acetylcholine. It induces a depolarizing block, but can also produce a non-depolarizing block in prolonged use or pseudocholinesterase deficiency. Non-depolarizing muscle relaxants are antagonists of acetylcholine, inducing a block by competition. Diseases-inducing situations of receptors upregulation expose to a great risk of hyperkalemia and cardiac arrest in case of succinylcholine use. On the other hand, the destruction of postsynaptic receptors, or acetylcholinesterase deficiency, exposes to prolonged neuromuscular blockade with non-depolarizing muscle relaxants. Instrumental monitoring of neuromuscular blockade and the reversal of a residual non-depolarizing block by anticholinesterases contribute to patient safety in anesthesia and intensive care.