KCNQ potassium channels: new targets for pulmonary vasodilator drugs?
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.
Gurney
Alison M
AM
Faculty of Life Sciences, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester, M13 9NT, UK, Alison. Alison@manchester.ac.uk
Joshi
Shreena
S
Manoury
Boris
B
D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D051656:KCNQ Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D051656:KCNQ Potassium Channels; D020033:Protein Isoforms; D014665:Vasodilator Agents