Calcium entry through stretch-inactivated ion channels in mdx myotubes.
Recent advances in understanding the molecular basis of human X-linked muscular dystrophies have come from the identification of dystrophin, a cytoskeletal protein associated with the surface membrane. Although there is little or virtually no dystrophin in affected individuals, 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+. In muscle from mdx mice, an animal model of the human disease, intracellular Ca2+ is elevated and associated with a high rate of protein degradation. 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-transducing 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. 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.
Franco
A
A
Department of Pharmacology, School of Medicine, University of California, San Francisco 94143-0450.
Lansman
J B
JB
D000818:Animals; D001464:Barium / Q000378:metabolism; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent; D002462:Cell Membrane / Q000502:physiology; D002463:Cell Membrane Permeability; D016189:Dystrophin; D004553:Electric Conductivity; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials; D051379:Mice; D009124:Muscle Proteins / Q000502:physiology; D009132:Muscles / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000503:physiopathology*
D002413:Cations, Divalent; D016189:Dystrophin; D007473:Ion Channels; D009124:Muscle Proteins; D001464:Barium; D002118:Calcium