Gurney Alison, Manoury Boris
Faculty of Life Sciences, The University of Manchester, Floor 2, Core Technology Facility, 46 Grafton Street, Manchester M139NT, UK.
Eur Biophys J. 2009 Mar;38(3):305-18. doi: 10.1007/s00249-008-0326-8. Epub 2008 May 1.
Two-pore domain (K(2P)) channels emerged about a decade ago and since then have been an expanding area of interest. This is because their biophysical and pharmacological properties make them good candidates to support background potassium currents and membrane potential in many cell types. There is clear evidence for TREK-1 and TASK-1 in the heart and these channels are likely to regulate cardiac action potential duration through their regulation by stretch, polyunsaturated fatty acids, pH, and neurotransmitters. TREK-1 may also have a critical role in mediating the vasodilator response of resistance arteries to polyunsaturated fatty acids, thus contributing to their protective effect on the cardiovascular system. TASK-1, on the other hand, is a strong candidate for a role in hypoxic vasoconstriction of pulmonary arteries. Many other members of the K(2P) channel family have been identified in the cardiovascular system, although their functional roles are still to be demonstrated. This review provides an up to date summary of what is known about the involvement of members of the K(2P) channel family in cells of the heart and arterial circulation. Our knowledge of their roles will improve with the rapidly increasing interest in them and as new selective pharmacological tools emerge. As their physiological roles emerge, the K(2P) family of potassium channels may offer promising therapeutic solutions to target cardiovascular diseases.
双孔结构域(K(2P))通道大约在十年前被发现,自那时起便成为一个不断扩展的研究热点领域。这是因为它们的生物物理和药理特性使其成为许多细胞类型中支持背景钾电流和膜电位的理想候选者。有明确证据表明心脏中存在TREK-1和TASK-1,并且这些通道可能通过受牵张、多不饱和脂肪酸、pH值和神经递质的调节来调控心脏动作电位的持续时间。TREK-1在介导阻力动脉对多不饱和脂肪酸的血管舒张反应中可能也起着关键作用,并因此对心血管系统产生保护作用。另一方面,TASK-1很可能在肺动脉的缺氧性血管收缩中发挥作用。K(2P)通道家族的许多其他成员已在心血管系统中被鉴定出来,尽管它们的功能作用仍有待证实。本综述提供了关于K(2P)通道家族成员在心脏和动脉循环细胞中的作用的最新总结。随着对它们的兴趣迅速增加以及新的选择性药理工具的出现,我们对其作用的认识将会得到提高。随着它们生理作用的显现,K(2P)钾通道家族可能为治疗心血管疾病提供有前景的治疗方案。