Role of the Ryanodine Receptor of Skeletal Muscle in Excitation-Contraction Coupling

In skeletal muscle, contraction is initiated by a depolarization of the transverse tubular membrane (t-tubule), which in turn signals the release of Ca from the sarcoplasmic reticulum (SR). A key protein involved in this process is the ryanodine receptor, an SR membrane protein of MW 450,000 that binds the alkaloid ryanodine with nanom-olar affinity and is present exclusively at the junction between t-tubule and SR mem-branes.1-4 The ryanodine receptor plays a dual role: Functionally, it is the putative Ca-release channel of the SR,4 and structurally, it is the major protein responsible for forming “bridges ” or “feet ” that anatomically connect t-tubule and SR.2,5 Here we demonstrate that the ryanodine receptor is steeply gated by both voltage and protons, and for the first time in vitro, we measured nonlinear capacitance (charge movement) that may be involved in the gating of this channel protein. We recently identified the 450,000-Da ryanodine receptor-feet protein (FIG. 1A) as the Ca-release channel of native SR.4,9,10 This was achieved using the planar bilayer recording technique and by comparing ligand-dependent gating, ionic selectivity, and pharmacology of purified ryanodine receptors to that of native Ca-release channels.11,2