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

Abstract

1 Effects of organic Ca²⁺-antagonists, verapamil and diltiazem, and cations, Ni²⁺, Mn²⁺, Co²⁺ and La³⁺ on Ca²⁺ current (I_Ca) 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 2 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 I_Ca 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 3 Divalent cations, Ni²⁺, Mn²⁺, Co²⁺ and the trivalent cation, La³⁺ inhibited I_Ca dose-dependently, but induced shifts of the I-V relationship to more positive voltages. The order of potency of inhibition of I_Ca among these cations was as follows; Ni²⁺ > La³⁺ > Mn²⁺ > Co²⁺ 4 Double reciprocal plots for peak I_Ca 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⁺ 5 Internal application of the organic Ca²⁺-antagonists (10⁻⁴m) inhibited I_Ca in a time-dependent manner to about 40–60% of the control. Ni²⁺, when applied internally, also depressed I_Ca 6 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 I_Ca in a similar manner to the organic Ca²⁺-antagonists, change the surface charge of the soma membrane.