Dihydropyridine calcium channel antagonists block and agonists potentiate high potassium contractures but not twitches in frog skeletal muscle.
The effects of two dihydropyridine calcium channel antagonists (nitrendipine and nifedipine) and two agonists (Bay K8644 and CGP-28392) were tested on high K(+)-induced contractures of frog's toe muscles. All four drugs depressed or blocked maximum contractures induced by 123 mM K+. Agonist effects, i.e., an increase in contracture amplitude, were found with smaller contractures produced by lower high K+ concentrations (i.e., 10, 20, and 25 mM). Bay K8644 produced its maximum agonist effect at 10(-7) M and only depressed contractures with 10(-6) M. CGP-28392 had its greatest agonist effect with 10(-9) M and had only antagonist effects with 10(-7) M or more. Nitrendipine had no agonist effects but nifedipine produced agonist effects with all concentrations tested (10(-9) to 10(-4) M). These results support previous results indicating that these contractures are initiated by extracellular Ca2+ ions entering via the voltage-sensitive, slow calcium channels in the t-tubules. The results obtained in the present study also are consistent with the known pharmacological effects of these drugs on calcium channels.
Frank
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Department of Pharmacology, University of Alberta, Edmonton, Canada.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D011894:Rana pipiens
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011725:Pyridines; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C040525:CGP 28392; D009568:Nitrendipine; D009543:Nifedipine; D011188:Potassium