Calcium entry through stretch-inactivated ion channels in mdx myotubes

Abstract

RECENT advances in understanding the molecular basis of human X-linked muscular dystrophies (for a review, see ref. 1) have come from the identification of dystrophin, a cytoskeletal protein associated with the surface membrane^2–4. Although there is little or virtually no dystrophin in affected individuals^5,6, it is not known how this causes muscle degeneration. One possibility is that the membrane of dystrophic muscle is weakened and becomes leaky to Ca²⁺ (refs 7–9). In muscle from mdx mice, an animal model of the human disease¹⁰, intracellular Ca²⁺ is elevated and associated with a high rate of protein degradation¹¹. The possibility that a lack of dystrophin alters the resting permeability of skeletal muscle to Ca²⁺ prompted us to compare Ca²⁺permeable ionic channels in muscle cells from normal and mdx mice. We now show that recordings of single-channel activity from mdx myotubes are dominated by the presence of Ca²⁺-permeable mechano-trans-ducing ion channels. Like similar channels in normal skeletal muscle, they are rarely open at rest, but open when the membrane is stretched by applying suction to the electrode^12–14. Other channels in mdx myotubes, however, are often open for extended periods of time at rest and close when suction is applied to the electrode. The results show a novel type of mechano-transducing ion channel in mdx myotubes that could provide a pathway for Ca²⁺ to leak into the cell.