Activation of vascular KCNQ (K v7) potassium channels reverses spasmogen-induced constrictor responses in rat basilar artery

Bharath K. Mani, Lioubov I. Brueggemann, Leanne L. Cribbs, Kenneth L. Byron

Research output: Contribution to journalReview article

31 Scopus citations

Abstract

BACKGROUND AND PURPOSE 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 v7) potassium channels in rat basilar artery myocytes, and determined the efficacy of K v7 channel activators in relieving spasmogen-induced basilar artery constriction. EXPERIMENTAL APPROACH Expression and function of K v7 channels in freshly isolated basilar artery myocytes were evaluated by reverse transcriptase polymerase chain reaction and whole-cell electrophysiological techniques. Functional responses to K v7 channel modulators were studied in intact artery segments using pressure myography. KEY RESULTS All five mammalian KCNQ subtypes (KCNQ1-5) were detected in the myocytes. K v currents were attributed to K v7 channel activity based on their voltage dependence of activation (V 0.5∼-34 mV), lack of inactivation, enhancement by flupirtine (a selective K v7 channel activator) and inhibition by 10,10-bis(pyridin-4-ylmethyl)anthracen-9-one (XE991; a selective K v7 channel blocker). XE991 depolarized the myocytes and constricted intact basilar arteries. Celecoxib, a clinically used anti-inflammatory drug, not only enhanced K v7 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 AND IMPLICATIONS K v7 channels are important determinants of basilar artery contractile status. Targeting the K v7 channels using flupirtine or celecoxib could provide a novel strategy to relieve basilar artery constriction in patients with cerebral vasospasm. LINKED ARTICLES To view two letters to the Editor regarding this article visit and

Original languageEnglish (US)
Pages (from-to)237-249
Number of pages13
JournalBritish Journal of Pharmacology
Volume164
Issue number2
DOIs
StatePublished - Sep 1 2011

Keywords

  • KCNQ
  • basilar artery
  • celecoxib
  • cerebral vasospasm
  • flupirtine
  • membrane voltage
  • potassium channel
  • vasoconstriction

ASJC Scopus subject areas

  • Pharmacology

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