Alteration of Sarcoplasmic Reticulum Ca 2 + Release in Skeletal Muscle from Calpain 3-Deficient Mice

Abstract

Mutations of Ca 2 + -activated proteases (calpains) cause muscular dystrophies. Nevertheless, the specific role of calpains in Ca 2 + signalling during the onset of dystrophies remains unclear. We investigated Ca 2 + handling in skeletal cells from calpain 3-deficient mice. [ Ca 2 + ] i responses to caffeine, a ryanodine receptor (RyR) agonist, were decreased in −/− myotubes and absent in −/− myoblasts. The −/− myotubes displayed smaller amplitudes of the Ca 2 + transients induced by cyclopiazonic acid in comparison to wild type cells. Inhibition of L-type Ca 2 + channels (LCC) suppressed the caffeine-induced [ Ca 2 + ] i responses in −/− myotubes. Hence, the absence of calpain 3 modifies the sarcoplasmic reticulum (SR) Ca 2 + 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 intracellular Ca 2 + signalling at a stage of cellular differentiation which is crucial for skeletal muscle regeneration.