Actions of calcium antagonists on calcium currents in Helix neurons. Specificity and potency

We have examined the effects of organic Ca++ channel blockade on calcium currents in Helix neurones, using a suction pipette technique which allows internal perfusion of the cell body and voltage clamp. In experiments on large cells with large currents, a microelectrode was used to measure membrane potential and provide the feedback potential for the voltage clamp. Calcium current was recorded after suppression of Na+ and K+ currents. The Ca++ conductance transports Ca++ and other divalent cations, such as Sr++, Ba++, Mn++, Zn++ and Cd++. Calcium current is temperature-dependent, and the Q10 of peak current was about 2.5. The organic Ca++ antagonists, verapamil, diltiazem, and nifedipine, inhibit calcium currents over the entire range of the current-voltage relationship. The effects are dose-dependent and there is no shifting in the current-voltage curves. Increases in extracellular Ca++ overcame the inhibitory action of the agents. Double reciprocal plots for peak calcium currents vs. external Ca++ concentrations in the presence or absence of diltiazem indicated competition with Ca++ at a common binding site. Intracellular application of diltiazem inhibited calcium currents.