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犬类心脏心室中Kv1.5是否存在功能相关性,以及这对I(Kur)阻滞剂的使用意味着什么?

Is there a functional correlate of Kv1.5 in the ventricle of canine heart and what would it mean for the use of I(Kur) blockers?

作者信息

Wettwer E

机构信息

Department of Pharmacology and Toxicology, Medical Faculty, Dresden University of Technology, Dresden, Germany.

出版信息

Br J Pharmacol. 2007 Nov;152(6):835-7. doi: 10.1038/sj.bjp.0707463. Epub 2007 Sep 17.

Abstract

The cardiac ultrarapid outward current I(Kur), encoded by KCNA5, is of special pharmacological interest, because it is considered to be atrium-specific. I(Kur) has therefore become a target in the therapy of atrial tachyarrhythmias. However, the concept of atrium specificity is only valid if a functional I(Kur) current is in fact absent from the ventricle. However, new work has detected a I(Kur)-like current in canine ventricular myocytes, sensitive to 4-aminopyridine and suppressed by the I(Kur) blocker DPO-1, findings that support the existence of a functional ventricular I(Kur). These indications are, however, indirect and more effort is needed to clarify unequivocally the putative role of an expectedly small I(Kur) component in the ventricle.

摘要

由KCNA5编码的心脏超快速外向电流I(Kur)具有特殊的药理学意义,因为它被认为是心房特异性的。因此,I(Kur)已成为治疗房性快速心律失常的一个靶点。然而,只有当心室中实际上不存在功能性I(Kur)电流时,心房特异性的概念才成立。然而,新的研究在犬心室肌细胞中检测到一种类似I(Kur)的电流,该电流对4-氨基吡啶敏感,并被I(Kur)阻滞剂DPO-1抑制,这些发现支持了功能性心室I(Kur)的存在。然而,这些迹象是间接的,需要更多的努力来明确阐明预期较小的I(Kur)成分在心室中的假定作用。

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Rab-GTPase-dependent endocytic recycling of Kv1.5 in atrial myocytes.Rab-GTP酶依赖性心房肌细胞中Kv1.5的内吞再循环
J Biol Chem. 2007 Oct 5;282(40):29612-20. doi: 10.1074/jbc.M704402200. Epub 2007 Aug 2.

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