Nilius B
Biomed Biochim Acta. 1984;43(12):1385-97.
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.
研究了新型二氢吡啶化合物BAY-K 8644对豚鼠乳头肌中钙依赖性慢动作电位的影响。在2×10⁻⁹至2×10⁻⁷mol/1的BAY-K浓度范围内，慢动作电位（sAP）的最大上升速度Umax增加，而在更高浓度时Umax又下降。在2.5×10⁻⁸mol/l（20mol/L K⁺）时获得半数最大效应。在相似浓度范围内，硝苯地平可拮抗Umax的增加。sAP的持续时间根据起搏间期而改变。在短起搏间期（至2秒）时，BAY-K使sAP缩短。BAY-K还在20mmol/l K⁺中诱导了小的超极化，并明显降低了阈电压。洗脱BAY-K总是导致sAP的超射延长。在40mmol/l K⁺时，BAY-K强烈增加Umax。Umax与膜电位之间的关系向Umax值增加的方向移动。在高于6×10⁻⁷mol/l的浓度下，BAY-K产生振荡性后去极化，表明药物诱导的钙超载。所有实验结果均与新型二氢吡啶化合物BAY-K 8644激活哺乳动物心室心肌钙通道的假说一致。
