Faculty of Life Sciences, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester, M13 9NT, UK, Alison.
Adv Exp Med Biol. 2010;661:405-17. doi: 10.1007/978-1-60761-500-2_26.
Smooth muscle cells regulate the diameter of pulmonary arteries and the resistance to blood flow in the pulmonary circulation. These cells are normally relaxed to maintain low intrinsic vessel tone, but are contracted in pulmonary arterial hypertension (PAH). Potassium channels in the smooth muscle cell help to maintain low tone by polarising the membrane and preventing Ca(2+) influx through voltage-operated Ca(2+) channels. There is a loss of K(+) channel activity in PAH, so drugs that open K(+) channels are predicted to have a beneficial effect, provided their action can be restricted to the pulmonary circulation. Here we review the myriad of K(+) channels that are expressed in pulmonary arteries and suggest the roles that each might play in regulating pulmonary artery tone. We conclude that members of the KCNQ family of K(+) channels, the most recent K(+) channels to be discovered in pulmonary artery, may be a useful therapeutic target for the treatment of PAH. KCNQ channels appear to be preferentially expressed in pulmonary arteries and drugs that modulate their activity have potent effects on pulmonary artery tone.
平滑肌细胞调节肺动脉的直径和肺循环中的血流阻力。这些细胞通常处于松弛状态，以维持低内在血管张力，但在肺动脉高压（PAH）中会收缩。平滑肌细胞中的钾通道通过极化细胞膜并防止电压门控钙通道中的 Ca(2+)内流来帮助维持低张力。PAH 中存在钾通道活性丧失，因此预计开放钾通道的药物会产生有益的效果，只要它们的作用可以局限于肺循环。在这里，我们回顾了在肺动脉中表达的众多钾通道，并提出了每种通道可能在调节肺动脉张力方面的作用。我们的结论是，最近在肺动脉中发现的 KCNQ 家族钾通道成员可能是治疗 PAH 的一个有用的治疗靶点。KCNQ 通道似乎优先在肺动脉中表达，调节其活性的药物对肺动脉张力有很强的作用。
