Calcium entry through stretch-inactivated ion channels in mdx myotubes

• Published in: Nature (London) 1990-04, Vol.344 (6267), p.670-673
• Main Authors: Franco, Alfredo, Lansman, Jeffry B
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Barium - metabolism; Biodegradation; Biological and medical sciences; Biomechanical Phenomena; calcium; Calcium (intracellular); Calcium - metabolism; Calcium channels; Calcium ions; Calcium permeability; Cations, Divalent; Cell Membrane - physiology; Cell Membrane Permeability; Cellular biology; Channel gating; Channel opening; Dystrophin; Dystrophy; Electric Conductivity; Electrodes; Humanities and Social Sciences; Ion channels; Ion Channels - physiology; Ions; letter; Medical research; Medical sciences; Membrane Potentials; Mice; multidisciplinary; Muscle Proteins - physiology; Muscles; Muscles - metabolism; Muscular dystrophy; Muscular Dystrophy, Animal - physiopathology; Musculoskeletal system; Myotubes; Neurology; Permeability; Potassium; Recording; Science; Science (multidisciplinary); Skeletal muscle; Suction
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/344670a0

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 Ca 2+ (refs 7–9). In muscle from mdx mice, an animal model of the human disease 10 , intracellular Ca 2+ is elevated and associated with a high rate of protein degradation 11 . The possibility that a lack of dystrophin alters the resting permeability of skeletal muscle to Ca 2+ prompted us to compare Ca 2+ 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 Ca 2+ -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 Ca 2+ to leak into the cell.