Abstract
The ryanodine receptor (RyR) ion channel releases Ca(2+) from intracellular stores by conducting Ca(2+) but also by recruiting neighboring RyRs to open, as RyRs are activated by micromolar levels of cytosolic Ca(2+). Using long single-RyR recordings of the cardiac isoform (RyR2), we conclude that Ca(2+) binding to the cytosolic face of RyR while the channel is closed determines the distribution of open times. This mechanism explains previous findings that RyR is not activated by its own fluxed Ca(2+). Our measurements also bolster previous findings that luminal [Ca(2+)] can affect both the cytosolic activation and inactivation sites and that RyR has different gating modes for the same ionic conditions.