Criddle D N, Greenwood I A, Weston A H
School of Biological Sciences, University of Manchester, UK.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Apr;349(4):422-30. doi: 10.1007/BF00170890.
In freshly-dispersed cells from rat mesenteric artery, levcromakalim (1 and 10 microM) induced a non-inactivating potassium current (IKCO), an event which was associated with increased current noise. IKCO was fully inhibited in the presence of 10 microM glibenclamide. Stationary fluctuation analysis of the current noise associated with IKCO induced by levcromakalim at a holding potential of -10 mV indicated that the unitary conductance of the underlying K-channels was 10.2 pS at 0 mV under the quasi-physiological conditions of the experiment. In isolated arterioles both levcromakalim (10 nM-10 microM) and nifedipine (10 nM-10 microM) each elicited full, concentration-dependent, parallel reductions of the increases in [Ca2+]i (assessed using fura-2) and tension induced by 10 microM noradrenaline. However, the effects of both drugs on KCl-induced increases in tension and in [Ca2+]i, did not follow a simple relationship. Levcromakalim relaxed KCl- and noradrenaline-induced sustained contractions with a similar potency. This was in contrast to nifedipine which was approximately 20 times more potent against KCl-induced contractions. It is concluded that levcromakalim relaxes rat mesenteric arterioles primarily by the opening of a small conductance, glibenclamide-sensitive K-channel. An additional action of levcromakalim is suggested by its relative inability to suppress the increase in [Ca2+]i produced by 30 mM K(+)-PSS.
在大鼠肠系膜动脉的新鲜分散细胞中，左旋克罗卡林（1和10微摩尔）诱导出一种非失活钾电流（IKCO），这一事件与电流噪声增加有关。在存在10微摩尔格列本脲的情况下，IKCO被完全抑制。在 -10 mV的钳制电位下，对左旋克罗卡林诱导的与IKCO相关的电流噪声进行稳态波动分析表明，在实验的准生理条件下，0 mV时基础钾通道的单位电导为10.2皮西门子。在分离的小动脉中，左旋克罗卡林（10纳摩尔 - 10微摩尔）和硝苯地平（10纳摩尔 - 10微摩尔）各自引起由10微摩尔去甲肾上腺素诱导的[Ca2+]i增加（使用fura - 2评估）和张力增加的完全、浓度依赖性、平行降低。然而，两种药物对氯化钾诱导的张力和[Ca2+]i增加的影响并不遵循简单的关系。左旋克罗卡林以相似的效力松弛氯化钾和去甲肾上腺素诱导的持续性收缩。这与硝苯地平形成对比，硝苯地平对氯化钾诱导的收缩的效力大约高20倍。得出的结论是，左旋克罗卡林主要通过开放一种小电导、格列本脲敏感的钾通道来松弛大鼠肠系膜小动脉。左旋克罗卡林相对无法抑制由30 mM K(+) - PSS产生的[Ca2+]i增加，提示其存在额外作用。
