Alteration of Sarcoplasmic ReticulumCa2+Release in Skeletal Muscle from Calpain 3-Deficient Mice

Abstract

Mutations ofCa2+-activated proteases (calpains) cause muscular dystrophies. Nevertheless, the specific role of calpains inCa2+signalling during the onset of dystrophies remains unclear. We investigatedCa2+handling in skeletal cells from calpain 3-deficient mice.[Ca2+]iresponses to caffeine, a ryanodine receptor (RyR) agonist, were decreased in −/− myotubes and absent in −/− myoblasts. The −/− myotubes displayed smaller amplitudes of theCa2+transients induced by cyclopiazonic acid in comparison to wild type cells. Inhibition of L-typeCa2+channels (LCC) suppressed the caffeine-induced[Ca2+]iresponses in −/− myotubes. Hence, the absence of calpain 3 modifies the sarcoplasmic reticulum (SR)Ca2+release, by a decrease of the SR content, an impairment of RyR signalling, and an increase of LCC activity. We propose that calpain 3-dependent proteolysis plays a role in activating support proteins of intracellularCa2+signalling at a stage of cellular differentiation which is crucial for skeletal muscle regeneration.