KCNQ Potassium Channels: New Targets for Pulmonary Vasodilator Drugs?
KCNQ Potassium Channels: New Targets for Pulmonary Vasodilator Drugs?
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DOI：
10.1007/978-1-60761-500-2_26
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发表时间：
2010-01-01
期刊：
影响因子：
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通讯作者：
Manoury, Boris
中科院分区：
文献类型：
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作者：
Gurney, Alison M.;Joshi, Shreena;Manoury, Boris
平滑肌细胞调节肺动脉的直径和肺循环中的血流阻力。这些细胞通常松弛以维持低的固有血管张力，但在肺动脉高压（PAH）中收缩。平滑肌细胞中的钾通道通过极化膜和阻止电压操纵的Ca2+通道的Ca2+内流来帮助维持低张力。PAH患者的K+通道活性丧失，因此预计开放K+通道的药物具有有益作用，前提是其作用可限于肺循环。在这里，我们回顾了无数的K+通道，在肺动脉中表达，并建议的作用，每一个可能发挥调节肺动脉张力。我们的结论是，KCNQ家族的K+通道，最新的K+通道被发现在肺动脉，可能是一个有用的治疗靶点，用于治疗肺动脉高压。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具有有效作用。
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 Ca2+ influx through voltage-operated Ca2+ 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.