Evidence for conformational coupling between two calcium channels.

Ryanodine receptor 1 (RyR1, the sarcoplasmic reticulum Ca(2+) release channel) and alpha(1S)dihydropyridine receptor (DHPR, the surface membrane voltage sensor) of skeletal muscle belong to separate membrane systems but are functionally and structurally linked. Four alpha(1S)DHPRs associated with the four identical subunits of a RyR form a tetrad. We treated skeletal muscle cell lines with ryanodine, at concentrations that block RyRs, and determined whether this treatment affects the distance between DHPRs in the tetrad. We find a substantial ( approximately 2-nm) shift in the alpha(1S)DHPR positions, indicating that ryanodine induces large conformational changes in the RyR1 cytoplasmic domain and that the alpha(1S)DHPR-RyR complex acts as a unit.