The muscle ryanodine receptor and its intrinsic Ca2+ channel activity

Abstract

In skeletal and cardiac muscle, contraction is initiated by the rapid release of Ca2+ ions from the intracellular membrane system, sarcoplasmic reticulum. Rapid-mixing vesicle ion flux and planar lipid bilayer-single-channel measurements have shown that Ca2+ release is mediated by a high-conductance, ligand-gated Ca2+ channel. Using the Ca2+ release-specific probe ryanodine, a 30 S protein complex composed of four polypeptides of Mr approximately 400,000 has been isolated. Reconstitution of the purified skeletal and cardiac muscle 30 S complexes into planar lipid bilayers induced single Ca2+ channel currents with conductance and gating kinetics similar to those of native Ca2+ release channels. Electron microscopy revealed structural similarity with the protein bridges ("feet") that span the transverse-tubule-sarcoplasmic reticulum junction. These results suggest that striated muscle contains an intracellular Ca2+ release channel that is identical with the ryanodine receptor and the transverse-tubule-sarcoplasmic reticulum spanning feet structures.