Ca2+ sparks as a plastic signal for skeletal muscle health, aging, and dystrophy.
Ca2+ sparks are the elementary units of intracellular Ca2+ signaling in striated muscle cells revealed as localized Ca2+ release events from sarcoplasmic reticulum (SR) by confocal microscopy. While Ca2+ sparks are well defined in cardiac muscle, there has been a general belief that these localized Ca2+ release events are rare in intact adult mammalian skeletal muscle. Several laboratories determined that Ca2+ sparks in mammalian skeletal muscle could only be observed in large numbers when the sarcolemmal membranes are permeabilized or the SR Ca2+ content is artificially manipulated, thus the cellular and molecular mechanisms underlying the regulation of Ca2+ sparks in skeletal muscle remain largely unexplored. Recently, we discovered that membrane deformation generated by osmotic stress induced a robust Ca2+ spark response confined in close spatial proximity to the sarcolemmal membrane in intact mouse muscle fibers. In addition to Ca2+ sparks, prolonged Ca2+ transients, termed Ca2+ bursts, are also identified in intact skeletal muscle. These induced Ca2+ release events are reversible and repeatable, revealing a plastic nature in young muscle fibers. In contrast, induced Ca2+ sparks in aged muscle are transient and cannot be re-stimulated. Dystrophic muscle fibers display uncontrolled Ca2+ sparks, where osmotic stress-induced Ca2+ sparks are not reversible and they are no longer spatially restricted to the sarcolemmal membrane. An understanding of the mechanisms that underlie generation of osmotic stress-induced Ca2+ sparks in skeletal muscle, and how these mechanisms are altered in pathology, will contribute to our understanding of the regulation of Ca2+ homeostasis in muscle physiology and pathophysiology.
Weisleder
Noah
N
Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Ma
Jian-jie
JJ
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D009137:Muscular Dystrophy, Animal / Q000503:physiopathology*; D009997:Osmotic Pressure; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D002118:Calcium