Effects of 2,3-butanedione monoxime on excitation-contraction coupling in frog twitch fibres.

10 and 30 mM 2,3-butanedione monoxime (BDM) applied extracellularly to voltage-clamped frog skeletal muscle twitch fibres suppressed both Ca2+ release flux and intramembranous charge movement. Both effects could be clearly separated. The early peak of the Ca2+ release flux was suppressed at every test voltage. The steady level attained at the end of a 100 ms clamp depolarization was relatively spared for lower depolarizing pulses, but was as suppressed as the peak at voltages above -20 mV. The intramembranous charge movement was affected mainly in the I gamma component. The drug had a distinct effect on the kinetics of the intramembranous charge movement current around the threshold for Ca2+ release. The three kinetic components of I gamma were simultaneously affected. For more positive depolarizations where the kinetic effect was not evident, the oxime had no significant effect on the charge moved. Under conditions in which I gamma was absent (i.e. stretched fibres, intracellular solutions containing 6 to 10 mM BAPTA), treatment with 10 mM BDM had a small, not significant suppressive effect on the maximum charge moved (Qmax), while it affected Ca2+ release significantly. When 10 mM BDM was applied in the presence of 0.2 mM tetracaine, the local anaesthetic-resistant Ca2+ release flux was not further suppressed by the oxime.