Upregulation of store-operated [Ca.sup.2+] entry in dystrophic mdx mouse muscle

Store-operated [Ca.sup.2+] entry (SOCE) is an important mechanism in virtually all cells. In adult skeletal muscle, this mechanism is highly specialized for the rapid delivery of [Ca.sup.2+] from the transverse tubule into the junctional cleft during periods of depleting [Ca.sup.2+] release. In dystrophic muscle fibers, SOCE may be a source of [Ca.sup.2+] overload, leading to cell necrosis. However, this possibility is yet to be examined in an adult fiber during [Ca.sup.2+] release. To examine this, [Ca.sup.2+] in the tubular system and cytoplasm were simultaneously imaged during direct release of [Ca.sup.2+] from sarcoplasmic reticulum (SR) in skeletal muscle fibers from healthy (wild-type, WT) and dystrophic mdx mouse. The mdx fibers were found to have normal activation and deactivation properties of SOCE. However, a depression of the cytoplasmic [Ca.sup.2+] transient in mdx compared with WT fibers was observed, as was a shift in the SOCE activation and deactivation thresholds to higher SR [Ca.sup.2+] concentrations ([[[Ca.sup.2+]].sub.SR]). The shift in SOCE activation and deactivation thresholds was accompanied by an approximately threefold increase in STIM1 and Orail proteins in dystrophic muscle. While the mdx fibers can introduce more [Ca.sup.2+] into the fiber for an equivalent depletion of [[[Ca.sup.2+]].sub.SR] via SOCE, it remains unclear whether this is deleterious. skeletal muscle; sarcoplasmic reticulum; muscular dystrophy; STIM1; Orail; excitation-contraction coupling doi: 10.1152/ajpcell.00524.2009.