Effect of ruthenium red on excitation-contraction coupling in frog skeletal muscle

The effects of ruthenium red (RR) on electrical and mechanical responses, and on Ca fluxes at rest and during potassium contracture (K contracture) in frog skeletal muscle were examined. By the treatment of single fibers with RR, the peak tensions of twitch and K contracture were inhibited, the degree of inhibition being dependent on the concentration of RR and on the duration of pretreatment. The inhibitory effect of RR on K contracture was pronounced at lower concentrations of K. The recovery of twitch tension from complete inhibition was observed several minutes after removal of RR by washing the fiber in normal Ringer solution, and was accelerated by brief exposure to 190 mM K solution. Caffeine contracture was not affected by RR. Moreover, resting and action potentials were not changed by RR except for an enhancement of a negative afterpotential. From these results, it is concluded that RR blocks excitation-contraction coupling (E-C coupling) in frog skeletal muscle. In addition, Ca influx, especially early rapid Ca influx, was markedly inhibited by RR, although the amount of self-exchangeable Ca was not significantly decreased. On the basis of these results, the sites and mechanism of RR action were discussed.