Role of Ca(2+) in injury-induced changes in sodium current in rat skeletal muscle.
Characteristics of voltage-dependent sodium current recorded from adult rat muscle fibers in loose patch mode were rapidly altered following nearby impalement with a microelectrode. Hyperpolarized shifts in the voltage dependence of activation and fast inactivation occurred within minutes. In addition, the amplitude of the maximal sodium current decreased within 30 min of impalement. Impalement triggered a sustained elevation of intracellular Ca(2+). However, buffering Ca(2+) by loading fibers with AM-BAPTA did not affect the hyperpolarized shifts in activation and inactivation, although it did prevent the reduction in current amplitude. Surprisingly, the rise in intracellular Ca(2+) occurred even in the absence of extracellular Ca(2+). This result indicated that the injury-induced Ca(2+) increase came from an intracellular source, but it was not blocked by an inhibitor of release from the sarcoplasmic reticulum, which suggested involvement of mitochondria. Ca(2+) release from mitochondria triggered by carbonyl cyanide 3-chlorophenylhydrazone was sufficient to cause a reduction in sodium current amplitude but had little effect of the voltage dependence of activation and fast inactivation. Our data suggest the effects of muscle injury can be separated into a Ca(2+)-dependent reduction in amplitude and a largely Ca(2+)-independent shift in activation and fast inactivation. Together, the impalement-induced changes in sodium current reduce the number of sodium channels available to open at the resting potential and may limit further depolarization and thus promote survival of muscle fibers following injury.
Filatov
Gregory N
GN
Department of Cell Biology and Neuroscience, University of California, Riverside, CA, USA.
Pinter
Martin J
MJ
Rich
Mark M
MM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000293:injuries* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*
D009124:Muscle Proteins; C466180:Scn4a protein, rat; D015222:Sodium Channels; D012964:Sodium; D002118:Calcium