Evidence for conformational coupling between two calcium channels

doi:10.1073/pnas.0404836101

Evidence for conformational coupling between two calcium channels

^*Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104; ^†Department of Anesthesia Research, Brigham and Women's Hospital, Boston, MA 02115; and ^‡Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616

Contributed by C. Franzini-Armstrong, July 7, 2004

Abstract

Ryanodine receptor 1 (RyR1, the sarcoplasmic reticulum Ca²⁺ release channel) and α_1Sdihydropyridine receptor (DHPR, the surface membrane voltage sensor) of skeletal muscle belong to separate membrane systems but are functionally and structurally linked. Four α_1SDHPRs 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 (≈2-nm) shift in the α_1SDHPR positions, indicating that ryanodine induces large conformational changes in the RyR1 cytoplasmic domain and that the α_1SDHPR-RyR complex acts as a unit.

Footnotes

↵ § To whom correspondence should be addressed at: B42 Anatomy-Chemistry Building, Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104-6058. E-mail: armstroc{at}mail.med.upenn.edu.
Abbreviations: CRU, calcium-release unit; DHPR, dihydropyridine receptor; RyR, ryanodine receptor; SR, sarcoplasmic reticulum.