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K(V)7 channels are ...
K(V)7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries
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- Hedegaard, E. R. (författare)
- Dept Biomed Pulm & Cardiovasc Pharmacol, Univ Aarhus, Aarhus, Denmark
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- Nielsen, B. D. (författare)
- Dept Biomed Pulm & Cardiovasc Pharmacol, Univ Aarhus, Aarhus, Denmark.; Dept Rheumatol, Aarhus Univ Hosp, Aarhus, Denmark
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- Kun, A. (författare)
- Dept Biomed Pulm & Cardiovasc Pharmacol, Univ Aarhus, Aarhus, Denmark
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- Hughes, A. D. (författare)
- Fac Med, Natl Heart & Lung Inst, Univ London Imperial Coll Sci Technol & Med, London, England
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- Kroigaard, C. (författare)
- Dept Biomed Pulm & Cardiovasc Pharmacol, Univ Aarhus, Aarhus, Denmark
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- Mogensen, S. (författare)
- Dept Biomed Pulm & Cardiovasc Pharmacol, Univ Aarhus, Aarhus, Denmark
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- Matchkov, V. V. (författare)
- Dept Biomed Pulm & Cardiovasc Pharmacol, Univ Aarhus, Aarhus, Denmark
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- Fröbert, Ole, 1964- (författare)
- Region Örebro län,Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, University of Aarhus, Aarhus, Denmark; Department of Cardiology, Örebro University Hospital, Örebro, Sweden
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- Simonsen, U. (författare)
- Dept Biomed Pulm & Cardiovasc Pharmacol, Univ Aarhus, Aarhus, Denmark
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Dept Biomed Pulm & Cardiovasc Pharmacol, Univ Aarhus, Aarhus, Denmark Dept Biomed Pulm & Cardiovasc Pharmacol, Univ Aarhus, Aarhus, Denmark; Dept Rheumatol, Aarhus Univ Hosp, Aarhus, Denmark (creator_code:org_t)
- 2013-12-10
- 2014
- Engelska.
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Ingår i: British Journal of Pharmacology. - : Wiley-Blackwell. - 0007-1188 .- 1476-5381. ; 171:1, s. 69-82
- Relaterad länk:
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- potassium channels
- K(V)7
- H2S
- adenosine
- hypoxia
- calcium
- coronary
- vasodilatation
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Hedegaard, E. R.
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Nielsen, B. D.
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Kun, A.
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Hughes, A. D.
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Kroigaard, C.
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Mogensen, S.
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Matchkov, V. V.
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Fröbert, Ole, 19 ...
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Simonsen, U.
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Örebro universitet