SUR2 subtype (A and B)-dependent differential activation of the cloned ATP-sensitive K+ channels by pinacidil and nicorandil
SUR2 subtype (A and B)-dependent differential activation of the cloned ATP-sensitive K+ channels by pinacidil and nicorandil
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DOI：
10.1038/sj.bjp.0701927
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发表时间：
1998-07-01
影响因子：
7.3
通讯作者：
Kurachi, Y
中科院分区：
文献类型：
--
作者：
Shindo, T;Yamada, M;Kurachi, Y
1经典的ATP敏感性钾通道（ATP sensitive K+ channel，ATP）由磺脲受体（sulfonylurea receptor，SUR）和内向整流钾通道亚基（inward rectifying Kf channel subunit，BIR/Kir6.2）组成。它们是称为K+通道开放剂的血管舒张剂（如吡那地尔和尼可地尔）的靶点。2为了检查吡那地尔和尼可地尔的组织选择性，我们在体外比较了这些药物对心脏类型的影响。（SUR 2A/Kir6.2）和血管平滑肌型（SUR 2B/Kir6.2）在HEK 293 T细胞（一种人胚肾细胞系）中异源表达的K-ATP通道，3在细胞贴附记录中，（移液管中145 mM Kf），吡那地尔和尼可地尔激活了两种转染细胞中的弱内向整流、格列本脲敏感的80 pS K+通道。4在全细胞配置中，吡那地尔在激活SUR 2B/Kir6.2和SUR 2A/Kir6.2通道方面显示出相似的效力（EC 50分别为相似于2和相似于10 μ M）。另一方面，尼可地尔激活SUR 2B/Kir6.2通道的效力是SUR 2A/Kir6.2通道的100倍以上。（EC 50分别类似于10 μ M和>500 μ M）。5因此，尼可地尔而不是吡那地尔优先激活含有SUR 2B的KATP通道。因为SUR 2A和SUR 2B仅在其C-末端的42个氨基酸中不同，强烈提示，SUR 2B的这一短部分可能在尼可地尔对血管型经典K-ATP通道的作用中发挥关键作用。
1 The classical ATP sensitive K+ (ATP) channels are composed of a sulphonylurea receptor (SUR) and an inward rectifying Kf channel subunit (BIR/Kir6.2). They are the targets of vasorelaxant agents called K+ channel openers, such as pinacidil and nicorandil.2 In order to examine the tissue selectivity of pinacidil and nicorandil, in vitro, we compared the effects of these agents on cardiac type (SUR2A/Kir6.2) and vascular smooth muscle type (SUR2B/Kir6.2) of the K-ATP channels heterologously expressed in HEK293T cells, a human embryonic kidney cell line, by using the patch-clamp method.3 In the cell-attached recordings (145 mM Kf in the pipette), pinacidil and nicorandil activated a weakly inwardly-rectifying, glibenclamide-sensitive 80 pS K+ channel in both the transfected cells.4 In the whole-cell configuration, pinacidil showed a similar potency in activating the SUR2B/Kir6.2 and SUR2A/Kir6.2 channels (EC50 of similar to 2 and similar to 10 mu M, respectively). On the other hand, nicorandil activated the SUR2B/Kir6.2 channel >100 times more potently than the SUR2A/Kir6.2 (EC50 of similar to 10 mu M and >500 mu M, respectively).5 Thus, nicorandil, but not pinacidil, preferentially activates the KATP channels containing SUR2B Because SUR2A and SUR2B are diverse only in 42 amino acids at their C-terminal ends, it is strongly suggested that this short part of SUR2B may play a critical role in the action of nicorandil on the vascular type classical K-ATP channel.