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

Abstract

Deficiency of δ-sarcoglycan (δ-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 possibility that the δ-SG deficiency may lead to alterations in ionic conductances, which may ultimately lead to myocyte damage. In cell-attached patches (with Ba²⁺ as the charge carrier), an ∼20-pS channel was observed 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-induced stretch and was reduced by GdCl₃ (>5 μM). 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 cytoskeleton. In intact Bio14.6 myotubes, the unidirectional basal Ca²⁺ influx was enhanced compared with control. This Ca²⁺ influx was sensitive to GdCl₃, signifying that stretch-activated cation channels may have been responsible for Ca²⁺ influx in Bio14.6 hamster myotubes. These results suggest a possible mechanism by which cell damage might occur in this animal model of muscular dystrophy.