Effects of calcium and strontium in the process of acetylcholine release from motor nerve endings

1. The effects of Ca and Sr ions on synchronous acetyleholine (ACh) secretion (the impulsive, physiologically functional form of secretion which produces an end‐plate potential in response to a single nerve impulse) and on asynchronous ACh secretion (the delayed, residual increase in miniature end‐plate potential frequency evoked by repetitive nerve impulses or by accumulation of intracellular divalent cations) were studied at frog neuromuscular junctions. 2. In a comparison of their extracellular effects, Ca was far more effective than Sr in supporting synchronous ACh secretion but less effective than Sr in mediating asynchronous release evoked by repetitive nerve impulses. 3. In studies of their intracellular effects, Sr and Ca were delivered to the nerve terminal cytoplasm using liposomes as a vehicle. Ca‐containing liposomes, although producing effects on asynchronous ACh secretion that were indistinguishable from those of equimolar Sr‐containing liposomes, were more effective than Sr‐containing liposomes in increasing synchronous release. 4. Extracellular Ca behaved as a potent competitve inhibitor of asynchronous, neurally evoked release mediated by Sr. In contrast, intracellular Ca (i.e. liposomal Ca), whilst increasing synchronous ACh release, failed to antagonize evoked asynchronous release. 5. The results demonstrate that synchronous and asynchronous secretion have different sensitivities to alterations in intracellular divalent cation concentrations. It is suggested that selectivity for Ca over Sr may occur at intraterminal sites responsible for synchronous ACh secretion but not at sites responsible for asynchronous ACh release. Furthermore, Ca appears to bind with high affinity as an antagonist at the external surface of the nerve ending. These results are discussed in conjunction with current theories of depolarization—secretion coupling.