Stretch-activated cation channels in skeletal muscle myotubes from sarcoglycan-deficient hamsters.
Deficiency of delta-sarcoglycan (delta-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 delta-SG deficiency may lead to alterations in ionic conductances, which may ultimately lead to myocyte damage. In cell-attached patches (with Ba(2+) as the charge carrier), an approximately 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 GdCl(3) (>5 microM). 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 Ca(2+) influx was enhanced compared with control. This Ca(2+) influx was sensitive to GdCl(3), signifying that stretch-activated cation channels may have been responsible for Ca(2+) 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.
Nakamura
T Y
TY
Department of Molecular Physiology, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.
Iwata
Y
Y
Sampaolesi
M
M
Hanada
H
H
Saito
N
N
Artman
M
M
Coetzee
W A
WA
Shigekawa
M
M
D000199:Actins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D015638:Cytochalasin D / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000172:deficiency*; D004553:Electric Conductivity; D004594:Electrophysiology; D005682:Gadolinium / Q000494:pharmacology; D006706:Homeostasis; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency*; D018482:Muscle, Skeletal / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D011108:Polymers / Q000378:metabolism; D012016:Reference Values; D049031:Sarcoglycans
D000199:Actins; D002412:Cations; D003598:Cytoskeletal Proteins; D007473:Ion Channels; D008562:Membrane Glycoproteins; D011108:Polymers; D049031:Sarcoglycans; D015638:Cytochalasin D; D005682:Gadolinium; C038958:gadolinium chloride; D002118:Calcium