CA2+ FEEDBACK ON QUANTAL CA2+ RELEASE INVOLVING RYANODINE RECEPTORS

The in fluence oi luminal and cytoplasmic Ca2+ on the ability oi ryano dine-sensitive stores to undergo multiple partial (''quantal'') releas es has been assessed, increased luminal Ca2+ levels do indeed modulate sarcoplasmic reticulum Ca2+ release by lowering the threshold agonist concentration required to elicit release, but the decrease in luminal Ca2+ that accompanies a partial release is not sufficient by itself t o terminate release. Similarly, an increase in cytoplasmic Ca2+ lowers the threshold agonist concentration required to elicit release; thus, the bulk cytoplasmic Ca2+ levels attained during a release would only simulate further release, not terminate it before it reached completi on. Very high cytoplasmic Ca2+ levels (1-3 mM) also triggered release but were unable to terminate release before reaching completion. Thus, even the high local cytoplasmic Ca2+ concentration that might accompa ny release would also not terminate release. It is concluded that Ca2 feedback can modulate release through ryanodine receptors but that it does not account for the properties of quantal release. The low affin ity inhibitor tetracaine induces a decrease in the extent of release t hat cannot be explained solely by heterogeneous caffeine sensitivity o i the stores, The results are interpreted in terms of a scheme that in cludes (i) heterogeneous sensitivity of stores, conferred in part by d ifferences in luminal Ca2+ content and (ii) adaptive behavior on the p art of individual ryanodine receptors.