title: Activation of vascular KCNQ (Kv7) potassium channels reverses spasmogen-induced constrictor responses in rat basilar artery.
abstract: OBJECTIVE
  Cerebral vasospasm is the persistent constriction of large conduit arteries in the base of the brain. This pathologically sustained contraction of the arterial myocytes has been attributed to locally elevated concentrations of vasoconstrictor agonists (spasmogens). We assessed the presence and function of KCNQ (K(v) 7) potassium channels in rat basilar artery myocytes, and determined the efficacy of K(v) 7 channel activators in relieving spasmogen-induced basilar artery constriction.
  
  
  METHODS
  Expression and function of K(v) 7 channels in freshly isolated basilar artery myocytes were evaluated by reverse transcriptase polymerase chain reaction and whole-cell electrophysiological techniques. Functional responses to K(v) 7 channel modulators were studied in intact artery segments using pressure myography.
  
  
  RESULTS
  All five mammalian KCNQ subtypes (KCNQ1-5) were detected in the myocytes. K(v) currents were attributed to K(v) 7 channel activity based on their voltage dependence of activation (V(0.5) ∼-34 mV), lack of inactivation, enhancement by flupirtine (a selective K(v) 7 channel activator) and inhibition by 10,10-bis(pyridin-4-ylmethyl)anthracen-9-one (XE991; a selective K(v) 7 channel blocker). XE991 depolarized the myocytes and constricted intact basilar arteries. Celecoxib, a clinically used anti-inflammatory drug, not only enhanced K(v) 7 currents but also inhibited voltage-sensitive Ca(2+) currents. In arteries pre-constricted with spasmogens, both celecoxib and flupirtine were more effective in dilating artery segments than was nimodipine, a selective L-type Ca(2+) channel blocker.
  
  
  CONCLUSIONS
  K(v) 7 channels are important determinants of basilar artery contractile status. Targeting the K(v) 7 channels using flupirtine or celecoxib could provide a novel strategy to relieve basilar artery constriction in patients with cerebral vasospasm.
  
  
  BACKGROUND
  To view two letters to the Editor regarding this article visit http://dx.doi.org/10.1111/j.1476-5381.2011.01454.x and http://dx.doi.org/10.1111/j.1476-5381.2011.01457.x.
authors.affiliation: Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Bharath K
authors.initials: BK
authors.lastname: Mani
authors.forename: Lioubov I
authors.initials: LI
authors.lastname: Brueggemann
authors.forename: Leanne L
authors.initials: LL
authors.lastname: Cribbs
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Byron
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology; D000068579:Celecoxib; D004594:Electrophysiology; D005786:Gene Expression Regulation / Q000502:physiology; D051656:KCNQ Potassium Channels / Q000819:agonists*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D020301:Vasospasm, Intracranial / Q000188:drug therapy*
chemical_list: D051656:KCNQ Potassium Channels; D011720:Pyrazoles; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009553:Nimodipine; D000068579:Celecoxib