Differential Proteolysis of the Full-Length Form of the L-Type Calcium Channel α1 Subunit by Calpain


Address correspondence and reprint requests to Dr. K. S. De Jongh at Department of Pharmacology, SJ-30, University of Washington, Seattle, WA 98195, U.S.A.


Abstract: This study examines the proteolysis of the carboxy terminal domain of the full-length (α1212) and truncated (α1190) forms of the rabbit skeletal muscle L-type calcium channel α1 subunit by calpain I and calpain II. Although both forms of the α1 subunit show little sensitivity to proteolysis by calpain II, α1212 is relatively more sensitive than α1190 to digestion by calpain I, the form of the enzyme regulated by micromolar concentrations of calcium. Calpain I cleaves a 37-kDa fragment from the C-terminus of α1212 in a time- and concentration-dependent manner and proteolysis is independent of the α1212 phosphorylation state. This proteolytic cleavage removes the major site of cyclic AMP-dependent phosphorylation from α1212 and may provide a mechanism for modifying the cyclic AMP-dependent regulation of L-type calcium channels in skeletal muscle.