Yoshitake I, Kubo K, Ikeda N, Kodama I, Toyama J, Yamada K
Nihon Yakurigaku Zasshi. 1986 Sep;88(3):179-87. doi: 10.1254/fpj.88.179.
Effects of KW-3049 on electrophysiological properties of the heart were examined using Langendorff-perfused hearts and superfused sinus nodal tissues of rabbits and superfused guinea-pig ventricular muscles. In rabbit hearts, KW-3049 at concentrations above 10(-7) M caused a dose-related prolongation of atrio-His bundle conduction time (AH), whereas His bundle-ventricular conduction time (HV) was unaffected. In spontaneously firing rabbit sinus nodal tissues, KW-3049 at concentrations above 10(-8) M prolonged cycle length significantly. At 10(-6) M, amplitude and the maximum upstroke velocity of sinus nodal action potential were decreased as well. In normally polarized guinea-pig ventricular muscles under 4 mM [K+]0, KW-3049 at concentrations above 10(-6) M shortened the action potential duration without affecting the resting membrane potential and the maximum upstroke velocity of action potential (Vmax). The Vmax of slow action potentials induced by isoproterenol at 10(-7) M was inhibited significantly by additional application of KW-3049 at concentrations above 10(-9) M. At above 10(-8) M, the amplitude and duration of slow action potentials were reduced significantly. The potency of this slow action potential inhibition by KW-3049 was slightly less than that of nifedipine, while it was 10 to 100 times greater than that of verapamil. Spontaneous activity of ventricular muscles induced by BaCl2 at 1 mM was abolished completely at 16 min after application of KW-3049 at 10(-7) M. These results suggest that KW-3049 may have a potent and selective inhibitory action on cardiac slow calcium channels.
使用Langendorff灌流心脏、家兔的超灌流窦房结组织和豚鼠的超灌流心室肌，研究了KW - 3049对心脏电生理特性的影响。在家兔心脏中，浓度高于10⁻⁷ M的KW - 3049可引起心房 - 希氏束传导时间（AH）呈剂量依赖性延长，而希氏束 - 心室传导时间（HV）不受影响。在自发放电的家兔窦房结组织中，浓度高于10⁻⁸ M的KW - 3049可显著延长周期长度。在10⁻⁶ M时，窦房结动作电位的幅度和最大上升速度也降低。在4 mM [K⁺]₀条件下正常极化的豚鼠心室肌中，浓度高于10⁻⁶ M的KW - 3049可缩短动作电位时程，而不影响静息膜电位和动作电位的最大上升速度（Vmax）。额外施加浓度高于10⁻⁹ M的KW - 3049可显著抑制10⁻⁷ M异丙肾上腺素诱导的慢动作电位的Vmax。在高于10⁻⁸ M时，慢动作电位的幅度和时程显著降低。KW - 3049对这种慢动作电位的抑制效力略低于硝苯地平，但其效力比维拉帕米大10至100倍。在施加10⁻⁷ M的KW - 3049后16分钟，1 mM BaCl₂诱导的心室肌自发活动完全消失。这些结果表明，KW - 3049可能对心脏慢钙通道具有强效和选择性抑制作用。
