Abstract
The activation of a unique Ca2+-induced Ca2+ release (CICR) mechanism via β-ryanodine receptors (RyRs) enhances transmitter exocytosis at the frog motor nerve terminals, once it is primed by repetitive Ca2+ entry. Hypertonicity is known to increase the basal frequency of miniature end-plate potentials (MEPPs) in frog neuromuscular junctions and also to increase Ca2+-activated ryanodine binding to α- and β-RyR purified from skeletal muscle (Murayama et al.,1998). Thus, it is possible that the hypertonicity-induced transmitter exocytosis results from the effect of hypertonicity to prime the mechanism of CICR. We have tested this hypothesis. The time course of priming, subsequent activation and inactivation of CICR was seen as a slow increase and subsequent decrease in the frequency of MEPP during continuous tetanus. The rate of slow rise in MEPP frequency by the tetanus was enhanced in one hour after the addition of sucrose in a low Ca2+, high Mg2+ solution. Hypertonicity also enhanced the quantal content of end-plate potentials (EPPs) induced by a single or tetanic stimulus. Ryanodine blocked these enhancements in the hypertonic solution. A small hypertonicity-induced transient increase in MEPP frequency during a tetanus even in a Ca2+ free, EGTA solution was also blocked by ryanodine. Results suggest that hypertonicity sets the condition for the activation of CICR and resulting enhancement of transmitter release. [Jpn J Physiol 54 Suppl:S160 (2004)]
