SUR1的新剪接变体改变了KATP通道的功能特性。

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Sakura H, Trapp S, Liss B, Ashcroft FM

SUR1的新剪接变体改变了KATP通道的功能特性。

《物理学报》1999年12月1日;521页:337-50。

PubMed ID

10581306 (PubMed视图

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摘要

1.atp敏感钾(KATP)通道由成孔(Kir6.x)和调节磺脲受体(SURx)亚基组成。我们从下丘脑cDNA文库中分离出一个新的SUR变体(SUR1bDelta33)。这种变体缺乏外显子33，并引入了移码，产生了缺少第二个核苷酸结合域(NBD2)的截断蛋白。它在下丘脑、中脑、心脏和分泌胰岛素的β细胞系MIN6中低水平表达。2.我们通过记录从表达这些亚基的非洲爪蟾卵母细胞中切除的膜片的宏观电流，检测了由Kir6.2和SUR1bDelta33组成的KATP通道的性质。我们还研究了在33外显子的开始(SUR1bT1)或结束(SUR1bT2)截断SUR1对KATP通道特性的影响。3.Kir6.2/SUR1bDelta33与野生型通道相比(Po = 0.3; Ki, 22 microM). However, Kir6.2/SUR1bT1 and Kir6.2/SUR1bT2 resembled the wild-type channel in their Po and ATP sensitivity. 4. Neither MgADP, nor the K+ channel opener diazoxide, enhanced Kir6.2/SUR1bDelta33, Kir6.2/SUR1bT1 or Kir6.2/SUR1bT2 currents, consistent with the idea that these agents require an intact NBD2 for their action. Sulphonylureas blocked KATP channels containing any of the three SUR variants, but in excised patches the extent of block was less than that for the wild-type channel. In intact cells, the extent of sulphonylurea block of Kir6.2/SUR1bDelta33 was greater than that in excised patches and was comparable to that found for wild-type channels. 5. Our results demonstrate that NBD2 is not essential for functional expression or sulphonylurea block, but is required for KATP channel activation by K+ channel openers and nucleotides. Some of the unusual properties of Kir6.2/SUR1bDelta33 resemble those reported for the KATP channel of ventromedial hypothalamic (VMH) neurones, but the fact that this mRNA is expressed at low levels in many other tissues makes it less likely that SUR1bDelta33 serves as the SUR subunit for the VMH KATP channel.

引用本文的药物库数据

药物靶点

药物	目标	种类	生物	药理作用	行动
氯甲苯噻嗪	atp敏感向内整流钾通道11	蛋白质	人类	是的	诱导物	细节