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.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D006372:Helix, Snails; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D013696:Temperature; D014700:Verapamil / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D007473:Ion Channels; D005711:Gallopamil; D014700:Verapamil; D004110:Diltiazem; D002118:Calcium