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

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Abstract
Most excitable cells maintain tight control of intracellular Ca2+ through coordinated interaction between plasma membrane and endoplasmic or sarcoplasmic reticulum. Quiescent sarcoplasmic reticulum Ca2+ release machinery is essential for the survival and normal function of skeletal muscle1,2,3. Here we show that subtle membrane deformations induce Ca2+ sparks in intact mammalian skeletal muscle. Spontaneous Ca2+ 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 Ca2+ sparks are essentially irreversible. Moreover, moderate exercise in mdx muscle alters the Ca2+ spark response. Thus, membrane-deformation-induced Ca2+ sparks have an important role in physiological and pathophysiological regulation of Ca2+ signalling, and uncontrolled Ca2+ spark activity in connection with chronic activation of store-operated Ca2+ entry may function as a dystrophic signal in mammalian skeletal muscle.