Desensitizing function of calcium mobilized by the postsynaptic neuronal-type nicotinic acetylcholine receptors at the neuromuscular junction

Neuronal-type nicotinic acetylcholine receptors (N-nAChR) are co-localized with muscle-type (M-)nAChR in the postjunctional endplate membrane of adult skeletal muscle fibers. The postsynaptic desensitizing functions of the N- nAChR at the neuromuscular junction and at single skeletal muscle cells hav e been investigated using aequorin luminescence and fluorescence confocal i maging. A biphasic elevation of local intracellular Ca2+ is elicited by pro longed nicotinic action at the mouse muscle endplates. The contractile fast and noncontractile slow Ca2+ components are operated by postsynaptic M- an d colocalized N-type aAChR, respectively. We have named the latter slow one RAMIC (receptor-activity modulating intracellular Ca2+). The N-nAChR are a ctivated by nicotine and choline, and RAMIC are antagonized by methyllycaco nitine and dihydro-beta-erythroidine. Neuromuscular functions may be regula ted by a dual aAChR system to maintain the normal postsynaptic excitability . Certain N-nAChR may be also endowed with the same functional role in the central nervous system.