DIFFERENTIAL BLOCKAGE OF CHARGE MOVEMENT COMPONENTS IN FROG CUT TWITCH FIBERS BY NIFEDIPINE

1. The effect of nifedipine on charge movement was studied in cut twitch fibres of Rana temporaria with a double Vaseline-gap voltage-clamp technique. The steady-state charge-voltage (Q-V) plot, in the absence or presence of nifedipine, was separated into Q-beta and Q-gamma components by fitting with a sum of two Boltzmann distribution functions. 2. When a fibre was held at -90 mV, low concentrations (around 20 nM) of nifedipine suppressed a larger fraction of Q-beta than Q-gamma. Higher concentrations of nifedipine suppressed Q-gamma more effectively than Q-beta, but even 2-mu-M-nifedipine did not suppress Q-beta and Q-gamma completely. Ten micromolar was required for complete suppression of Q-gamma. Nifedipine thus suppressed Q-beta and Q-gamma with different dose dependencies. 3. When the holding potential was changed to -70 mV, some Q-beta and Q-gamma were inactivated. Low concentrations (around 20 nM) of nifedipine still suppressed a larger fraction of the mobile Q-beta than the mobile Q-gamma. Higher concentrations of nifedipine also suppressed Q-gamma more effectively than Q-beta, but 2-mu-M-nifedipine was sufficient to suppress Q-gamma completely. Hence, at this slightly depolarized holding potential, nifedipine also suppressed Q-beta and Q-gamma with different dose dependencies. 4. A portion of Q-beta appeared to be resistant to the action of nifedipine. At -70 mV, the blockage of the nifedipine-sensitive portion of Q-beta appeared to saturate at 2-mu-M of the drug. At -90 mV, the nifedipine-resistant portion of Q-beta was more difficult to identify, because the blockage of the nifedipine-sensitive portion of Q-beta did not saturate at 2-mu-M. 5. Based on double-reciprocal plots for the dose-response relationships, the half-blocking concentration of nifedipine for Q-beta was found to be 14-19 nM at -90 mV and < 13 nM at -70 mV, whereas that for Q-gamma was approximately 1.6-mu-M at -90 mV and 120 nM at -70 mV. Thus, nifedipine suppressed Q-gamma in a voltage-dependent manner, but its suppression of Q-beta was much less voltage dependent. 6. It was demonstrated that the enhancement in the blockage of charge movement by maintained depolarization could not be achieved by depolarizing pulses lasting up to hundreds of milliseconds. 7. The difference in the half-blocking concentrations of nifedipine for Q-beta and Q-gamma implies that Q-beta and Q-gamma cannot be tightly coupled.