title: Pharmacological dissection of K(v)7.1 channels in systemic and pulmonary arteries.
abstract: OBJECTIVE
  The aim of this study was to characterize the functional impact of KCNQ1-encoded voltage-dependent potassium channels (K(v)7.1) in the vasculature.
  
  
  METHODS
  Mesenteric arteries, intrapulmonary arteries and thoracic aortae were isolated from adult rats. K(v)7.1 channel expression was established by fluorescence immunocytochemistry. Wire myography determined functionality of these channels in response to selective blockers and activators. Xenopus oocytes expressing K(v)7.1 channels were used to assess the effectiveness of selective K(v)7.1 channel blockers.
  
  
  RESULTS
  K(v)7.1 channels were identified in arterial myocytes by immunocytochemistry. K(v)7.1 blockers HMR1556, L-768,673 (10 µM) and JNJ39490282 (JNJ282; 1 µM) had no contractile effects in arteries, whereas the pan-K(v)7 channel blocker linopirdine (10 µM) evoked robust contractions. Application of two compounds purported to activate K(v)7.1 channels, L-364 373 (R-L3) and mefenamic acid, relaxed mesenteric arteries preconstricted by methoxamine. These responses were reversed by HMR1556 or L-768,673 but not JNJ282. Similar effects were observed in the thoracic aorta and intrapulmonary arteries.
  
  
  CONCLUSIONS
  In contrast to previous assumptions, K(v)7.1 channels expressed in arterial myocytes are functional ion channels. Although these channels do not appear to contribute to resting vascular tone, K(v)7.1 activators were effective vasorelaxants.
authors.affiliation: Division of Biomedical Sciences: Ion Channels and Cell Signalling Group, St George's, University of London, London, UK.
authors.forename: Preet S
authors.initials: PS
authors.lastname: Chadha
authors.forename: Friederike
authors.initials: F
authors.lastname: Zunke
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Davis
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Jepps
authors.forename: Joannes T M
authors.initials: JT
authors.lastname: Linders
authors.forename: Michael
authors.initials: M
authors.lastname: Schwake
authors.forename: Rob
authors.initials: R
authors.lastname: Towart
authors.forename: Iain A
authors.initials: IA
authors.lastname: Greenwood
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051656:KCNQ Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051657:KCNQ1 Potassium Channel / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C117367:KCNQ4 protein, human; C412231:KCNQ5 protein, human; C496911:Kcnq1 protein, rat; D026902:Potassium Channel Blockers; D011994:Recombinant Proteins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents