ACTIONS OF VERAPAMIL, DILTIAZEM AND OTHER DIVALENT CATIONS ON THE CALCIUM‐CURRENT OF Helix NEURONES

Abstract

Effects of organic Ca2+‐antagonists, verapamil and diltiazem, and cations, Ni2+, Mn2+, Co2+ and La3+ on Ca2+ current (ICa) separated from other ionic currents in a Helix neurone were studied. A suction pipette technique which allows internal perfusion of the cell body and voltage clamp was used Verapamil and diltiazem (10−6‐10−4m) increased the threshold, and decreased both the amplitude and rate of rise of the soma Ca2+‐spike. Both agents inhibited ICa over the entire range of the current‐voltage (I‐V) relationship dose‐dependently, without shifting the threshold of the I‐V relationship. Increases in external Ca2+ overcame the inhibitory action of the agents Divalent cations, Ni2+, Mn2+, Co2+ and the trivalent cation, La3+ inhibited ICa dose‐dependently, but induced shifts of the I‐V relationship to more positive voltages. The order of potency of inhibition of ICa among these cations was as follows; Ni2+ > La3+ > Mn2+ > Co2+ Double reciprocal plots for peak ICa versus external Ca2+ concentrations in the presence or absence of both organic and inorganic Ca2+‐antagonists intersect at the ordinate. Results indicate that both organic and inorganic Ca2+‐antagonists compete for Ca2+ at the common binding site for Ca2+ Internal application of the organic Ca2+‐antagonists (10−4m) inhibited ICa in a time‐dependent manner to about 40–60% of the control. Ni2+, when applied internally, also depressed ICa The results provide evidence that organic Ca2+‐antagonists occupy the binding site for Ca2+ in a competitive manner at the surface of the soma membrane of the Helix neurone, while divalent and trivalent cations, in addition to inhibiting ICa in a similar manner to the organic Ca2+‐antagonists, change the surface charge of the soma membrane. 1981 British Pharmacological Society