Na+-Ca2+ exchange induces low Na(+)contracture in frog skeletal muscle fibers after partial inhibition of sarcoplasmic reticulum Ca2+-ATPase

Contractile responses due to reduction in external sodium concentration ([N a+](o)) were investigated in twitch skeletal muscle fibers of frog semitend inosus. Experiments were conducted after partial inhibition of sarcoplasmic reticulum Ca2+-ATPase by cyclopiazonic acid (CPA). In the absence of CPA, Na+ withdrawal failed to produce any change in resting tension. In the pres ence of CPA (2-10 mu M), [Na+](o) reduction induced a transient contracture without a significant change in the resting membrane potential. The amplit ude of the contracture displayed a step dependence on [Na+](o) was increase d by K+-free medium and was prevented in Ca2+-free medium. This contracture was inhibited by various blockers of the Na+-Ca2+ exchange but was little affected by inhibitors of sarcolemmal Ca2+-ATPase or mitochondria. When sar coplasmic reticulum function was impaired, low-Naf solutions caused no cont racture. These results provide evidence that skeletal muscle fibers possess a functional Na+-Ca2+ exchange which can mediate sufficient Ca2+ entry to activate contraction by triggering Ca2+ release from sarcoplasmic reticulum when the sodium electrochemical gradient is reduced, and sarcoplasmic reti culum Ca2+-ATPase is partially inhibited. This indicates that when the sarc oplasmic reticulum Ca2+-ATPase is working (no CPA), Ca2+ fluxes produced by the exchanger are buffered by the sarcoplasmic reticulum. Thus the Na+-Ca2 + exchange may be one of the factors determining sarcoplasmic reticulum Ca2 + content and thence the magnitude of the release of Ca2+ from the sarcopla smic reticulum.