Skeletal muscle ryanodine receptor is a redox sensor with a well defined redox potential that is sensitive to channel modulators

Hyperreactive sulfhydryl groups associated with the Ca2+ release protein fr om sarcoplasmic reticulum are shown to have a well defined reduction potent ial that is sensitive to the cellular environment. Ca2+ channel activators lower the redox potential of the ryanodine receptor, which favors the oxida tion of thiols and the opening of the Ca2+ release protein. In contrast, ch annel inhibitors increase the redox potential, which favors the reduction o f disulfides and the closure of the release protein. Modulation of redox po tential of reactive thiols may be a general control mechanism by which sarc oplasmic/endoplasmic reticulum, ryanodine receptors/IP3 receptors, control cytoplasmic Ca2+ concentrations.