Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists

Abstract

Single cardiac transmembranous Ca channels [from guinea pig and frog hearts] have 3 modes of gating behavior in the absence of drugs, expressed as current records with brief openings (mode 1), with no openings because of channel unavailability (mode 0 or null mode), and with long-lasting openings and very brief closings that appear only rarely (mode 2). The dihydropyridine Ca agonist Bay K 8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate] enhances Ca channel current by promoting mode 2, while the Ca antagonists nitrendipine and nimodipine inhibit the current by favoring mode 0. [Implications with respect to the use of these agents in the treatment of human cardiovascular disorders are presented.].