RT Journal Article SR Electronic T1 Ca2+ Feedback on “Quantal” Ca2+Release Involving Ryanodine Receptors JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1124 OP 1130 DO 10.1124/mol.52.6.1124 VO 52 IS 6 A1 Christine Dettbarn A1 Philip Palade YR 1997 UL http://molpharm.aspetjournals.org/content/52/6/1124.abstract AB The influence of luminal and cytoplasmic Ca2+ on the ability of ryanodine-sensitive stores to undergo multiple partial (“quantal”) releases 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 to 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 stimulate further release, not terminate it before it reached completion. 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 accompany 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 affinity inhibitor tetracaine induces a decrease in the extent of release that cannot be explained solely by heterogeneous caffeine sensitivity of the stores. The results are interpreted in terms of a scheme that includes (i) heterogeneous sensitivity of stores, conferred in part by differences in luminal Ca2+ content and (ii) adaptive behavior on the part of individual ryanodine receptors.