Structures of the colossal RyR1 calcium release channel

Ryanodine receptors (RyRs) are intracellular cation channels that mediate the rapid and voluminous release of Ca2+ from the sarcoplasmic reticulum (SR) as required for excitation-contraction coupling in cardiac and skeletal muscle. Understanding of the architecture and gating of RyRs has advanced dramatically over the past two years, due to the publication of high resolution cryo-electron microscopy (cryoEM) reconstructions and associated atomic models of multiple functional states of the skeletal muscle receptor, RyR1. Here we review recent advances in our understanding of RyR architecture and gating, and highlight remaining gaps in understanding which we anticipate will soon be filled.