Activation of the voltage-dependent Ca2+ channel in rat heart cells by dihydropyridine derivatives.
The two dihydropyridines Bay K8644 and CGP 28392 increase 45Ca2+ influx in cultured rat cardiac cells with half-maximal effects at 2 nM and 30 nM respectively at a membrane potential of -75 mV. This stimulation of Ca2+ uptake is inhibited by nitrendipine, verapamil and bepridil. Ca2+ channel activation produced by Bay K8644 and CGP 28392 has been compared with Ca2+ channel activation produced by depolarization. There is no addition between the effects of drugs activating the Ca2+ channel and the effects of depolarization suggesting that Bay K8644 and CGP 28392 work preferentially on polarized membranes. 45Ca2+ flux experiments yielded results which are in excellent agreement with electrophysiological and contraction data obtained with the same cells in culture. Dose-response curves for the physiological effects of the drugs are observed over the same range of concentrations as their inhibition of [3H]nitrendipine binding to its receptor.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D015764:Bepridil; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007473:Ion Channels / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D007473:Ion Channels; D011725:Pyridines; D011759:Pyrrolidines; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015764:Bepridil; C040525:CGP 28392; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium