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Pulmonary vasoconstrictor action of KCNQ potassium channel blockers

Joshi, Shreena and Balan, Prabhu and Gurney, Alison M. (2006) Pulmonary vasoconstrictor action of KCNQ potassium channel blockers. Respiratory Research, 7 (31). ISSN 1465-9921

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    Abstract

    KCNQ channels have been widely studied in the nervous system, heart and inner ear, where they have important physiological functions. Recent reports indicate that KCNQ channels may also be expressed in portal vein where they are suggested to influence spontaneous contractile activity. The biophysical properties of K+ currents mediated by KCNQ channels resemble a current underlying the resting K+ conductance and resting potential of pulmonary artery smooth muscle cells. We therefore investigated a possible role of KCNQ channels in regulating the function of pulmonary arteries by determining the ability of the selective KCNQ channel blockers, linopirdine and XE991, to promote pulmonary vasoconstriction. Linopirdine and XE991 both contracted rat and mouse pulmonary arteries but had little effect on mesenteric arteries. In each case the maximum contraction was almost as large as the response to 50 mM K+. Linopirdine had an EC50 of around 1 μM and XE991 was almost 10-fold more potent. Neither removal of the endothelium nor exposure to phentolamine or α,β-methylene ATP, to block α1-adrenoceptors or P2X receptors, respectively, affected the contraction. Contraction was abolished in Ca2+-free solution and in the presence of 1 μM nifedipine or 10 μM levcromakalim.

    Item type: Article
    ID code: 3121
    Keywords: KCNQ channels, respiratory resaerch, heart, potassium channel blockers, physiology, Physiology, Biology, Pulmonary and Respiratory Medicine
    Subjects: Science > Physiology
    Science > Natural history > Biology
    Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences > Physiology and Pharmacology
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    Depositing user: Strathprints Administrator
    Date Deposited: 16 Apr 2007
    Last modified: 05 Sep 2014 13:21
    URI: http://strathprints.strath.ac.uk/id/eprint/3121

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