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(γ) 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(γ) 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(γ) 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 (Q(max)), 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.