4.6 Article

Molecular Mechanisms of the Inhibitory Effects of Clonidine on Vascular Adenosine Triphosphate-Sensitive Potassium Channels

期刊

ANESTHESIA AND ANALGESIA
卷 113, 期 6, 页码 1374-1380

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1213/ANE.0b013e3182321142

关键词

-

资金

  1. Japan Society for the Promotion of Science, Tokyo, Japan [C 15591636]
  2. Grants-in-Aid for Scientific Research [23792350, 22591748, 23592994] Funding Source: KAKEN

向作者/读者索取更多资源

BACKGROUND: We investigated the effects of the imidazoline-derived alpha 2-adrenoceptor agonist clonidine on vascular adenosine triphosphate-sensitive potassium (K(ATP)) channel activity in rat vascular smooth muscle cells and recombinant vascular K(ATP) channels transiently expressed in COS-7 cells. METHODS: Using the patch-clamp method, we investigated the effects of clonidine on the following: (1) native vascular K(ATP) channels; (2) recombinant K(ATP) channels with different combinations of various types of inwardly rectifying potassium channel (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor (SUR1, 2A, 2B) subunits; (3) SUR-deficient channels derived from a truncated isoform of the Kir6.2 subunit (Kir6.2 Delta C36 channels); and (4) mutant Kir6.2 Delta C36 channels with diminished sensitivity to ATP (Kir6.2 Delta C36-K185Q channels). RESULTS: Clonidine (>= 3 x 10(-8) M) inhibited native K(ATP) channel activity in cell-attached configurations with a half-maximal inhibitory concentration value of 1.21 x 10(-6) M and in inside-out configurations with a half-maximal inhibitory concentration value of 0.89 x 10(-6) M. With similar potency, clonidine (10(-6) or 10(-3) M) also inhibited the activities of various recombinant SUR/Kir6.0 K(ATP) channels, the Kir6.2 Delta C36 channel, and the Kir6.2 Delta C36-K185Q channel. CONCLUSIONS: Clinically relevant concentrations of clonidine inhibit K(ATP) channel activity in vascular smooth muscle cells. This inhibition seems to be the result of its effect on the Kir6.0 subunit and not on the SUR subunit. (Anesth Analg 2011;113:1374-80)

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据