Uncontrolled calcium sparks act as a dystrophic signal for mammalian skeletal muscle

Most excitable cells maintain tight control of intracellular Ca 2 + through coordinated interaction between plasma membrane and endoplasmic or sarcoplasmic reticulum. Quiescent sarcoplasmic reticulum Ca 2 + release machinery is essential for the survival and normal function of skeletal muscle1-3. Here we show that subtle membrane deformations induce Ca 2 + sparks in intact mammalian skeletal muscle. Spontaneous Ca 2 + sparks can be reversibly induced by osmotic shock, and participate in a normal physiological response to exercise. In dystrophic muscle with fragile membrane integrity, stress-induced Ca 2 + sparks are essentially irreversible. Moreover, moderate exercise in mdx muscle alters the Ca 2 + spark response. Thus, membrane-deformation-induced Ca 2 + sparks have an important role in physiological and pathophysiological regulation of Ca 2 + signalling, and uncontrolled Ca 2 + spark activity in connection with chronic activation of store-operated Ca 2 + entry may function as a dystrophic signal in mammalian skeletal muscle.