Stretch-activated cation channels in skeletal muscle myotubes from sarcoglycan-deficient hamsters

Deficiency of delta -sarcoglycan (delta -SG), a component of the dystrophin -glycoprotein complex, causes cardiomyopathy and skeletal muscle dystrophy in Bio14.6 hamsters. Using cultured myotubes prepared from skeletal muscle of normal and Bio14.6 hamsters (J2N-k strain), we investigated the possibil ity that the delta -SG deficiency may lead to alterations in ionic conducta nces, which may ultimately lead to myocyte damage. In cell-attached patches (with Ba2+ as the charge carrier), an similar to 20-pS channel was observe d in both control and Bio14.6 myotubes. This channel is also permeable to K + and Na+ but not to Cl-. Channel activity was increased by pressure-induce d stretch and was reduced by GdCl3 (>5 muM). The basal open probability of this channel was fourfold higher in Bio14.6 myotubes, with longer open and shorter closed times. This was mimicked by depolymerization of the actin cy toskeleton. In intact Bio14.6 myotubes, the unidirectional basal Ca2+ influ x was enhanced compared with control. This Ca2+ influx was sensitive to GdC l3, signifying that stretch-activated cation channels may have been respons ible for Ca2+ influx in Bio14.6 hamster myotubes. These results suggest a p ossible mechanism by which cell damage might occur in this animal model of muscular dystrophy.