title: Uncontrolled calcium sparks act as a dystrophic signal for mammalian skeletal muscle.
abstract: 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 muscle. 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.
authors.affiliation: Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Noah
authors.initials: N
authors.lastname: Weisleder
authors.forename: Claude
authors.initials: C
authors.lastname: Collet
authors.forename: Jingsong
authors.initials: J
authors.lastname: Zhou
authors.forename: Yi
authors.initials: Y
authors.lastname: Chu
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hirata
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhao
authors.forename: Zui
authors.initials: Z
authors.lastname: Pan
authors.forename: Marco
authors.initials: M
authors.lastname: Brotto
authors.forename: Heping
authors.initials: H
authors.lastname: Cheng
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000502:physiology*; D009137:Muscular Dystrophy, Animal / Q000503:physiopathology*; D010805:Physical Conditioning, Animal / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology*