Ca~(2+)sparks are the elementary units of intracellular Ca~(2+)signaling in striated musclecells revealed as localized Ca~(2+)release events from sarcoplasmic reticulum(SR)byconfocal microscopy.While Ca~(2+)sparks are well defined in cardiac muscle,therehas been a general belief that these localized Ca~(2+)release events are rare in intactadult mammalian skeletal muscle.Several laboratories determined that Ca~(2+)sparksin mammalian skeletal muscle could only be observed in large numbers when thesarcolemmal membranes are permeabilized or the SR Ca~(2+)content is artificiallymanipulated,thus the cellular and molecular mechanisms underlying the regula-tion of Ca~(2+)sparks in skeletal muscle remain largely unexplored.Recently,wediscovered that membrane deformation generated by osmotic stress induced arobust Ca~(2+)spark response confined in close spatial proximity to the sarcolemmalmembrane in intact mouse muscle fibers.In addition to Ca~(2+)sparks,prolongedCa~(2+)transients,termed Ca~(2+)bursts,are also identified in intact skeletal muscle.These induced Ca~(2+)release events are reversible and repeatable,revealing a plas-tic nature in young muscle fibers.In contrast,induced Ca~(2+)sparks in aged muscleare transient and cannot be re-stimulated.Dystrophic muscle fibers display un-controlled Ca~(2+)sparks,where osmotic stress-induced Ca~(2+)sparks are not revers-ible and they are no longer spatially restricted to the sarcolemmal membrane.Anunderstanding of the mechanisms that underlie generation of osmotic stress-induced Ca~(2+)sparks in skeletal muscle,and how these mechanisms are altered inpathology,will contribute to our understanding of the regulation of Ca~(2+)homeo-stasis in muscle physiology and pathophysiology. Ca 2+ sparks are the elementary units of intracellular Ca 2+ signaling in striated muscle cells revealed as localized Ca 2+ release events from sarcoplasmic reticulum (SR) by confocal microscopy.While Ca 2+ sparks are well defined in cardiac muscle, therehas been a general belief that these localized Ca ~ (2+) release events are rare in intactadult mammalian skeletal muscle. Laboratory laboratories that that Ca ~ (2+) sparksin mammalian skeletal muscle could only be observed in large numbers when thesarcolemmal membranes are permeabilized or the SR Ca ~ (2+) content is artificiallymanipulated, thus the cellular and molecular mechanisms underlying the regula tion of Ca ~ (2+) sparks in skeletal muscle populations largely unexplored.Recently, wediscovered that membrane deformation generated by osmotic stress induced arobust Ca ~ (2+) spark response confined in close spatial proximity to the sarcolemmalmembrane in intact mouse muscle fibers. addition to Ca ~ (2+) sparks, prolonged Ca ~ (2+) transients, termed Ca ~ (2+ ) bursts, also also identified in intact skeletal muscle.These induced Ca ~ (2+) release events are reversible and repeatable, revealing a plas-tic nature in young muscle fibers. In contrast, induced Ca ~ (2+) sparks in aged muscleare transient and can not be re-stimulated.Dystrophic muscle fibers display un-controlled Ca ~ (2+) sparks, where osmotic stress-induced Ca ~ (2+) sparks are not revers-ible and they are no longer spatially restricted to the An understanding of the mechanisms that underlie generation of osmotic stress-induced Ca ~ (2+) sparks in skeletal muscle, and how these mechanisms are altered in pathology, will contribute to our understanding of the regulation of Ca ~ (2+) homeo -stasis in muscle physiology and pathophysiology.