title: Stimulation of Ca-dependent action potentials in mammalian ventricular myocardium by a novel dihydropyridine.
abstract: Effects of the novel dihydropyridine compound BAY-K 8644 on Ca-dependent slow action potentials in guinea pig papillary muscles were studied. The maximum upstroke velocity Umax of slow action potentials (sAP) increased in concentrations between 2 X 10(-9) and 2 X 10(-7) mol/1 BAY-K whereas at higher concentrations Umax decreased again. Half maximum effects were obtained at 2.5 X 10(-8) mol/l (20 mol/L K+). The increase in Umax could be antagonized by nifedipine in a similar range of concentrations. The duration of sAP was changed depending on the pacing interval. At short pacing intervals (up to 2 s) sAP were abbreviated by BAY-K. BAY-K also induced a small hyperpolarization in 20 mmol/l K+ and lowered the threshold voltage distinctly. Washing out of BAY-K resulted always in an overshooting lengthening of sAP. BAY-K strongly increased Umax at 40 mmol/l K+. The relationship between Umax and the membrane potential was shifted to increased Umax values. At concentrations higher than 6 X 10(-7) mol/l BAY-K produced oscillatory afterdepolarizations indicating a drug-induced Ca overload. All the experimental findings are consistent with the hypothesis that the novel dihydropyridine compound BAY-K 8644 activates Ca-channels in the mammalian ventricular myocardium.
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D007473:Ion Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium