POTASSIUM CHANNEL OPENERS ACT THROUGH AN ACTIVATION OF ATP-SENSITIVE K+ CHANNELS IN GUINEA-PIG CARDIAC MYOCYTES
POTASSIUM CHANNEL OPENERS ACT THROUGH AN ACTIVATION OF ATP-SENSITIVE K+ CHANNELS IN GUINEA-PIG CARDIAC MYOCYTES
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DOI：
10.1007/bf00582134
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发表时间：
1989-09-01
影响因子：
4.5
通讯作者：
CAVERO, I
中科院分区：
文献类型：
--
作者：
ESCANDE, D;THURINGER, D;CAVERO, I
在之前的文章（Escande et al. 1988 a）中，我们已经证明，克罗卡林（BRL 34915）是一种钾通道开放剂（PCO），是心肌细胞中ATP敏感性K+通道的有效激活剂。在本文中，在膜片钳分离的心肌细胞中研究了与色满卡林化学上无关的另外两种钾通道开放剂RP 49356和吡那地尔对K+通道的影响。在全细胞构型中，在50 μ M TTX和3 μ M尼群地平或3 mM钴存在下记录K+电流。与cromakalim一样，RP 49356或吡那地尔在33 - 35 ° C下激活了与时间无关的外向电流。C，但不在19 - 21 °。在-60 ~+60 mV的电位范围内，对电压的依赖性很小。其幅度是激动剂浓度的函数，例如，其为2.1 ± 0.01。0.4 nA，+60 mV，30 μ M RP 49356和4.3 ±。0.8 nA，300 μ M。在控制条件下，格列本脲，在胰腺和心脏细胞中的K+-ATP通道的阻滞剂，既不影响内向整流，iK 1，也不延迟K+电流，iK。在3 μ M时，格列本脲完全阻止300 μ M RP 49356或吡那地尔的作用。在较低浓度下，格列本脲部分抵消了PCO对K+电流的激活。在细胞附着配置中，外部施加RP 49356或吡那地尔引起大通道的开放，其在高K+外部介质中在0 mV左右逆转。在由内而外的贴剂中，RP 49356或吡那地尔都通过增加通道保持开放状态的时间来激活K+-ATP通道。可以得出结论，像cromakalim，RP 49356和吡那地尔是心肌细胞中K+-ATP通道的有效激活剂。
In a previous article (Escande et al. 1988a), we have shown that cromakalim (BRL 34915), a potassium channel opener (PCO), is a potent activator of ATP-sensitive K+ channels in cardiac cells. In the present article, the influence of K+ channels of two other potassium channel openers chemically unrelated to cromakalim, RP 49356 and pinacidil, has been investigated in patch-clamped isolated cardiac myocytes. In the whole-cell configuration, K+ currents were recorded in the presence of 50 .mu.M TTX and 3 .mu.M nitrendipine or 3 mM cobalt. Like cromakalim, RP 49356 or pinacidil activated a time-independent outward current at 33-35.degree. C but not at 19-21.degree. C, which showed little voltage-dependency in the potential range -60 to +60 mV. Its amplitude was a function of the agonist concentration, e.g. it was 2.1 .+-. 0.4 nA at +60 mV with 30 .mu.M RP 49356 and 4.3 .+-. 0.8 nA with 300 .mu.M. In control conditions, glibenclamide, a blocker of K+-ATP channels in pancreatic and heart cells, affected neither the inward rectifier, iK1, nor the delayed K+ current, iK. At 3 .mu.M, glibenclamide fully prevented the effects of 300 .mu.M RP 49356 or pinacidil. At lower concentrations, glibenclamide partially counteracted the activation by PCOs of a K+ current. In the cell-attached configuration, externally applied RP 49356 or pinacidil caused opening of large channels which reversed around 0 mV in a high K+ external medium. In inside-out patches, both RP 49356 or pinacidil activated K+-ATP channels by increasing the time period for which the channels remained in the open state. It is concluded that, like cromakalim, RP 49356 and pinacidil are potent activators of K+-ATP channels in cardiac myocytes.