DHPR activation underlies SR Ca release induced by osmotic stress in isolated rat skeletal muscle fibers

Skeletal muscle swells as a consequence of intense activity and gradually returns to its original volume after cessation of exercise (Sjogaard et al., 1985; Peeze Binkhorst et al., 1990; Watson et al., 1993; Raja et al., 2006). Swelling occurs due to an accumulation of metabolites within the cytosol and a consequent increase in osmolarity, which drives the entry of water from the extracellular space (Nagesser et al., 1992; Sejersted and Sjogaard, 2000; Lannergren et al., 2002; Raja et al., 2006). Recent studies have sought to establish the functional consequences of cell volume changes in mammalian skeletal muscle; e.g., in mouse flexor digitorum brevis (FDB) fibers, transient swelling induced by exposure to hypoosmotic Tyrode’s solution ([NaCl] decreased: 140 to 70 mM) induced localized SR Ca release (LCR), which was sustained for several minutes (Wang et al., 2005; Weisleder et al., 2006; Martins et al., 2008; Weisleder and Ma, 2008). This form of LCR occurred mostly at the cell periphery and was reported to involve both Ca