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K(V)7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries
Univ Aarhus, Dept Biomed Pulm & Cardiovasc Pharmacol, Aarhus, Denmark..
Univ Aarhus, Dept Biomed Pulm & Cardiovasc Pharmacol, Aarhus, Denmark.;Aarhus Univ Hosp, Dept Rheumatol, DK-8000 Aarhus, Denmark..
Univ Aarhus, Dept Biomed Pulm & Cardiovasc Pharmacol, Aarhus, Denmark..
Univ London Imperial Coll Sci Technol & Med, Fac Med, Natl Heart & Lung Inst, London SW7 2AZ, England..
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2014 (English)In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 171, no 1, 69-82 p.Article in journal (Refereed) Published
Abstract [en]

Background and PurposeHypoxia causes vasodilatation of coronary arteries, but the underlying mechanisms are poorly understood. We hypothesized that hypoxia reduces intracellular Ca2+ concentration ([Ca2+](i)) by opening of K channels and release of H2S. Experimental ApproachPorcine coronary arteries without endothelium were mounted for measurement of isometric tension and [Ca2+](i), and the expression of voltage-gated K channels K(V)7 channels (encoded by KCNQ genes) and large-conductance calcium-activated K channels (K(Ca)1.1) was examined. Voltage clamp assessed the role of K(V)7 channels in hypoxia. Key ResultsGradual reduction of oxygen concentration from 95 to 1% dilated the precontracted coronary arteries and this was associated with reduced [Ca2+](i) in PGF(2) (10M)-contracted arteries whereas no fall in [Ca2+](i) was observed in 30mM K-contracted arteries. Blockers of ATP-sensitive voltage-gated potassium channels and K(Ca)1.1 inhibited hypoxia-induced dilatation in PGF(2)-contracted arteries; this inhibition was more marked in the presence of the K(v)7 channel blockers, XE991 and linopirdine, while a K(V)7.1 blocker, failed to change hypoxic vasodilatation. XE991 also inhibited H2S- and adenosine-induced vasodilatation. PCR revealed the expression of K(V)7.1, K(V)7.4, K(V)7.5 and K(Ca)1.1 channels, and K(Ca)1.1, K(V)7.4 and K(V)7.5 were also identified by immunoblotting. Voltage clamp studies showed the XE991-sensitive current was more marked in hypoxic conditions. ConclusionThe K(V)7.4 and K(V)7.5 channels, which we identified in the coronary arteries, appear to have a major role in hypoxia-induced vasodilatation. The voltage clamp results further support the involvement of K(V)7 channels in this vasodilatation. Activation of these K(V)7 channels may be induced by H2S and adenosine.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014. Vol. 171, no 1, 69-82 p.
Keyword [en]
potassium channels, K(V)7, H2S, adenosine, hypoxia, calcium, coronary, vasodilatation
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:oru:diva-56436DOI: 10.1111/bph.12424ISI: 000328014400006PubMedID: 24111896Scopus ID: 2-s2.0-84890290283OAI: oai:DiVA.org:oru-56436DiVA: diva2:1082351
Note

Funding Agencies:

Danish Heart Foundation

Danish Medical Research Council

Available from: 2017-03-16 Created: 2017-03-16 Last updated: 2017-03-16Bibliographically approved

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