The ryanodine receptor: advances in structure and organization

Ryanodine receptor Ca 2+ release channels (RyR) are the largest intracellular ion channels known. The primary physiological role of the RyR is to provide a ligand-regulated pathway for the release of stored Ca 2+ to regulate a diverse array of cellular processes. This article highlights advances in RyR channel structure, shedding new light on closed-to-open channel transitions and on the mechanisms of channel gating in health and disease. We also evaluate how recent studies on the self-association of RyR in situ have revealed a potential relationship between the dynamic organization of channels in clusters and the termination of the regenerative feedback of Ca 2+ -induced Ca 2+ release. Lastly, we consider how this information might impact on the development of new RyR-focused therapies.