Ryanodine Receptor Calcium Release Channels

The ryanodine receptors (RyRs) are a family of Ca2+ release channels found on intracellular Ca2+ storage/release organelles. The RyR channels are ubiquitously expressed in many types of cells and participate in a variety of important Ca2+ signaling phenomena (neurotransmission, secretion, etc.). In striated muscle, the RyR channels represent the primary pathway for Ca2+ release during the excitation-contraction coupling process. In general, the signals that activate the RyR channels are known (e.g., sarcolemmal Ca2+ influx or depolarization), but the specific mechanisms involved are still being debated. The signals that modulate and/or turn off the RyR channels remain ambiguous and the mechanisms involved unclear. Over the last decade, studies of RyR-mediated Ca2+ release have taken many forms and have steadily advanced our knowledge. This robust field, however, is not without controversial ideas and contradictory results. Controversies surrounding the complex Ca2+ regulation of single RyR channels receive particular attention here. In addition, a large body of information is synthesized into a focused perspective of single RyR channel function. The present status of the single RyR channel field and its likely future directions are also discussed.