Mechanosensitive Ion Channels in Skeletal Muscle from Normal and Dystrophic Mice

摘要

1 We examined the activity of single mechanosensitive ion channels in recordingsfrom cell-attached patches on myoblasts, differentiated myotubes and acutely isolated skeletal muscle fibres from wild-type and mdx and dy mutant mice. The experiments were concerned with the role of these channels in the, pathophysiology of muscular dystrophy. (2) The predominant form of channel activity recorded with physiological saline in the patch electrode arose from an 25 pS mechanosensitive ion channel. Channel activity Co was similar in undifferentiated myoblasts isolated from all three strains of mice. By contrast, channel activity in n%dx myotubes was 3-4 times greater than in either wild-type or dy myotubes and arose from a novel mode of mechanosensitive gating. (3) Single mechanosensitive channels in acutely isolated flexor digitorum brevis fibres had properties indistinguishable from those of muscle cells grown in tissue culture. The channel open probability in mdx fibres was 2 times greater than the activity recorded from wild-type fibres. The overall level of activity in fibres, however, was roughly an order of magnitude smaller than in myoblasts or myotubes. (4) Histological examination of the flexor digitorum brevis fibres from mdx mice showed no evidence of myonecrosis or regenerating fibres, suggesting that the elevated channel activity in dystrophin-deficient muscle precedes the onset of fibre degeneration. (5) An early step in the dystrophic process of the mdx mouse, which leads to pathophysiological Ca2+ entry, may be an alteration in the mechanisms that regulate mechanosensitive ion channel activity. The absence of the cytoskeletal protein, dystrophin, from skeletal muscle is the primary genetic defect in Duchenne muscular dystrophy.