Conventional calcium channel mediates asynchronous acetylcholine release by motor nerve impulses

Abstract

STIMULATION of the motor nerve, in addition to producing the synchronous, impulsive release of acetylcholine (ACh) that is recorded electrophysiologically as the endplate potential (e.p.p.)¹, also elicits a delayed, asynchronous discharge of ACh quanta that appears as increases in miniature endplate potential (m.e.p.p.) frequencies^2–4. The synchronous release of ACh is mediated by the movement of Ca²⁺ through specific conductance channels activated by depolarisation of the motor nerve ending (for reviews see refs 1, 5 and 6). Although asynchronous release is dependent in some fashion on extracellular (Ca²⁺) (ref. 4) there seems to be a controversy as to the precise nature of the ionic pathway responsible for this dependence. For example, although it has been suggested that asynchronous evoked release is mediated by residual Ca²⁺ that enters through the traditional Ca²⁺ conductance pathway³, results with Mg²⁺ have suggested the contrary⁴. Specifically, it has been shown that Mg²⁺, rather than antagonising the asynchronous release of ACh in Ca²⁺ solutions, (as would be expected if Ca²⁺ moved through the same conductance pathway for both forms of release^7–10), actually enhanced the asynchronous discharge of ACh quanta⁴. The present study investigated the effects of the conventional Ca²⁺ antagonists, Co²⁺ and Mg²⁺, on the asynchronous evoked release of ACh. The results demonstrate that after brief, repetitive stimulation, both ions competitively antagonise asynchronous ACh release in a manner similar to their respective antagonism of synchronous release^7,10. We conclude that Ca²⁺ supports both dispersed and synchronous ACh release through the same conductance pathway.