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Abstract

A comparative study of the blockade of calcium-dependent action potentials by verapamil, nifedipine and nimodipine in ventricular muscle.

M Hachisu and A J Pappano
Journal of Pharmacology and Experimental Therapeutics April 1983, 225 (1) 112-120;
M Hachisu
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Abstract

The electrophysiological and chemical properties of the Ca++-channel blocking drugs verapamil, nifedipine and nimodipine were compared. In avian ventricular muscle depolarized by 25 mM K+-saline, the primary Na+ conductance was inactivated and the peak of action potential varied by 30 mV/10-fold change in extracellular Ca++. A double reciprocal plot of the maximum rate of rise vs. [Ca++]0(-1) yielded a straight line, a result consistent with the surface density hypothesis for the electrogenic permeation of cell membranes by Ca++. Verapamil, nifedipine and nimodipine caused the peak of action potential to deviate significantly from its Ca++-electrode property. Verapamil, but not nifedipine or nimodipine, blocked the Ca++-dependent action potential in a frequency-dependent manner. However, the dihydrophyridines (nifedipine and nimodipine) and verapamil were similar insofar as they inhibited the maximum rate of rise of the Ca++-dependent action potential competitively at concentrations less than or equal to 10(-6) M. These results are consistent with the hypothesis that low concentrations of these drugs inhibit the Ca++-dependent action potential by reducing the secondary inward current which is carried largely by Ca++. At higher concentrations, blockade of the maximum rate of rise by all of the Ca++-channel blocking drugs could not be described as competitive, noncompetitive or uncompetitive. The inability to describe the equilibrium actions of high concentrations of verapamil, nifedipine and nimodipine in such terms may arise from drug effects on membrane currents in addition to secondary inward current.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 225, Issue 1
1 Apr 1983
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Abstract

A comparative study of the blockade of calcium-dependent action potentials by verapamil, nifedipine and nimodipine in ventricular muscle.

M Hachisu and A J Pappano
Journal of Pharmacology and Experimental Therapeutics April 1, 1983, 225 (1) 112-120;

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Abstract

A comparative study of the blockade of calcium-dependent action potentials by verapamil, nifedipine and nimodipine in ventricular muscle.

M Hachisu and A J Pappano
Journal of Pharmacology and Experimental Therapeutics April 1, 1983, 225 (1) 112-120;
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