How does succinylcholine produce muscle relaxation?
Succinylcholine is a depolarizing neuromuscular blocking drug that structurally consists of two acetylcholine mole-cules linked through acetate methyl groups. Because of its structural similarity to acetylcholine, it acts as an agonist at the nicotinic acetylcholine receptor. When two succinyl-choline molecules bind to the α proteins of the receptor, it becomes activated as though two acetylcholine molecules were activating the receptors (agonism). The receptors open for the ingress of sodium ions, and the endplate becomes depolarized, which leads to muscle contraction in the same fashion.
The activity that predominantly differentiates succinyl-choline from acetylcholine agonism occurs after the initial depolarization. Whereas acetylcholine is hydrolyzed by acetylcholinesterase in milliseconds, succinylcholine is not. Succinylcholine remains active at the endplate for several minutes, maintaining endplate depolarization. The end-plate cannot repolarize until succinylcholine leaves the neu-romuscular junction. The sodium channels of the muscle cell, when activated by a depolarized endplate leading to the cell’s depolarization, can remain in the activated (open) state for only 2 milliseconds. The sodium channels distal to the endplate return immediately to the ready (closed) state, while the sodium channels proximal to the endplate (peri-junctional) remain influenced by the charge of the depo-larized endplate. They cannot fully return to the ready (closed) state, nor are they able to remain activated (open), because sodium channels can activate for only 2 milli-seconds. The perijunctional sodium channels are neither active nor ready to transmit a wave of depolarization to the myocytes, because they must fully close first before they can reopen (activate). Therefore, transmission is blocked with a depolarized endplate surrounded by a perijunc-tional area that has not fully repolarized and a repolarized (relaxed) myocyte.