Abstract
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+ homeo-stasis in muscle physiology and pathophysiology.
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Weisleder, N., Ma, Jj. Ca2+ sparks as a plastic signal for skeletal muscle health, aging, and dystrophy. Acta Pharmacol Sin 27, 791–798 (2006). https://doi.org/10.1111/j.1745-7254.2006.00384.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00384.x
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