@article {Dettbarn1124, author = {Christine Dettbarn and Philip Palade}, title = {Ca2+ Feedback on {\textquotedblleft}Quantal{\textquotedblright} Ca2+Release Involving Ryanodine Receptors}, volume = {52}, number = {6}, pages = {1124--1130}, year = {1997}, doi = {10.1124/mol.52.6.1124}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The influence of luminal and cytoplasmic Ca2+ on the ability of ryanodine-sensitive stores to undergo multiple partial ({\textquotedblleft}quantal{\textquotedblright}) 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{\textendash}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.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/52/6/1124}, eprint = {https://molpharm.aspetjournals.org/content/52/6/1124.full.pdf}, journal = {Molecular Pharmacology} }