Satoh H
Department of Pharmacology, Nara Medical University, Japan.
J Cardiovasc Pharmacol. 1993 Dec;22(6):863-8. doi: 10.1097/00005344-199312000-00014.
Electrophysiologic effects of ATP-sensitive K+ channel openers (cromakalim, pinacidil, and nicorandil) in single rabbit sino-atrial (SA) node cells were examined by a whole-cell voltage- and current-clamp technique. Cromakalim (> 30 microM), pinacidil (> 1 microM), and nicorandil (> 500 microM) caused a negative chronotropic effect. At low concentrations, the maximum diastolic potential was hyperpolarized and the maximum rate of depolarization was enhanced, but at high concentrations, both were reversed and action potential amplitude (APA) was decreased significantly. Pinacidil (> 30 microM) and nicorandil (> 3 microM) prolonged AP duration (APD), but cromakalim did not affect it. In whole-cell voltage-clamp experiments, cromakalim (100 microM), pinacidil (> 30 microM), and nicorandil (> 300 microM) inhibited the Ca2+ current significantly but had little or no effect on the delayed rectifying K+ current and the hyperpolarization-activated inward current. Glibenclamide (1 microM) did not antagonize the effects of K+ channel openers on Ca2+ current and APs. These results indicate that the K+ channel openers have direct inhibitory actions on spontaneous APs and Ca2+ current in rabbit SA node cells (but K+ current was unaffected), resulting in decreased pacemaker activity.
采用全细胞膜片钳电压钳和电流钳技术，研究了ATP敏感性钾通道开放剂（克罗卡林、匹那地尔和尼可地尔）对单个家兔窦房结细胞的电生理效应。克罗卡林（>30μM）、匹那地尔（>1μM）和尼可地尔（>500μM）可产生负性变时作用。在低浓度时，最大舒张电位超极化，最大去极化速率加快，但在高浓度时，两者均发生逆转，动作电位幅度（APA）显著降低。匹那地尔（>30μM）和尼可地尔（>3μM）可延长动作电位时程（APD），但克罗卡林对其无影响。在全细胞膜片钳实验中，克罗卡林（100μM）、匹那地尔（>30μM）和尼可地尔（>300μM）可显著抑制Ca2+电流，但对延迟整流钾电流和超极化激活内向电流几乎没有影响或无影响。格列本脲（1μM）不能拮抗钾通道开放剂对Ca2+电流和动作电位的作用。这些结果表明，钾通道开放剂对家兔窦房结细胞的自发性动作电位和Ca2+电流具有直接抑制作用（但对钾电流无影响），导致起搏活性降低。
