Genetic defects in the hotspot of inwardly rectifying K(+) (Kir) channels and their metabolic consequences: a review.
Genetic defects in the hotspot of inwardly rectifying K(+) (Kir) channels and their metabolic consequences: a review.
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DOI：
10.1016/j.ymgme.2011.10.004
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发表时间：
2012-01
影响因子：
3.8
通讯作者：
Pillers, De-Ann M.
中科院分区：
文献类型：
--
作者：
Pattnaik, Bikash R.;Asuma, Matti P.;Spott, Ryan;Pillers, De-Ann M.
抑制整流钾通道（Kir）对于维持正常的钾稳态和静息膜电位是必不可少的。因此，Kir通道中的突变引起从心力衰竭到肾、眼、胰腺和神经异常的衰弱性疾病。在结构上，Kir通道由两个跨膜结构域、含有选择性过滤器的成孔环和两个细胞质极性尾组成。在细胞质结构内，氨基酸序列簇形成调节结构域，其与细胞代谢物相互作用以控制通道的打开和关闭。在这篇综述中，我们提出了一个概述Kir通道的功能和最近的进展，在选定的Kir通道突变的特征在于和附近的C-末端胞质的热点域。通道功能的丧失或获得导致器官衰竭的分子机制为这组重要的通道病提供了潜在的靶向治疗干预机会。
Inwardly rectifying potassium (Kir) channels are essential for maintaining normal potassium homeostasis and the resting membrane potential. As a consequence, mutations in Kir channels cause debilitating diseases ranging from cardiac failure to renal, ocular, pancreatic, and neurological abnormalities. Structurally, Kir channels consist of two trans-membrane domains, a pore-forming loop that contains the selectivity filter and two cytoplasmic polar tails. Within the cytoplasmic structure, clusters of amino acid sequences form regulatory domains that interact with cellular metabolites to control the opening and closing of the channel. In this review, we present an overview of Kir channel function and recent progress in the characterization of selected Kir channel mutations that lie in and near a C-terminal cytoplasmic ‘hotspot’ domain. The resultant molecular mechanisms by which the loss or gain of channel function leads to organ failure provide potential opportunities for targeted therapeutic interventions for this important group of channelopathies.
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