Modal shifts in acetylcholine receptor channel gating confer subunit-dependent desensitization

During the transition from embryonic to adult skeletal muscle, a decreased mean channel open time and accelerated desensitization of nicotinic acetylcholine (ACh) receptors result from the substitution of an epsilon subunit for gamma. A single ACh receptor channel of the embryonic type, expressed in Xenopus oocytes, interconverts between gating modes of short and long open time, whereas the adult receptor channel resides almost exclusively in the gating mode with short open time. Differences in the fraction of time spent in either gating mode account for the subunit dependence of both receptor open time and desensitization. Therefore, developmental changes in the kinetics of muscle ACh receptors may be imparted through subunit-dependent stabilization of intrinsic gating modes.