Dataset Information

KV 7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries.

ABSTRACT:

Background and purpose

Hypoxia causes vasodilatation of coronary arteries, but the underlying mechanisms are poorly understood. We hypothesized that hypoxia reduces intracellular Ca(2+) concentration ([Ca(2+)](i)) by opening of K channels and release of H?S.

Experimental approach

Porcine coronary arteries without endothelium were mounted for measurement of isometric tension and [Ca(2+)](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 results

Gradual reduction of oxygen concentration from 95 to 1% dilated the precontracted coronary arteries and this was associated with reduced [Ca(2+)](i) in PGF(2?) (10 ?M)-contracted arteries whereas no fall in [Ca(2+)](i) was observed in 30 mM K-contracted arteries. Blockers of ATP-sensitive voltage-gated potassium channels and K(Ca)1.1 inhibited hypoxia-induced dilatation in PGF2? -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 H?S- 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.

Conclusion

The 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 H?S and adenosine.

SUBMITTER: Hedegaard ER

PROVIDER: S-EPMC3874697 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Publications

KV 7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries.

Hedegaard E R ER Nielsen B D BD Kun A A Hughes A D AD Krøigaard C C Mogensen S S Matchkov V V VV Fröbert O O Simonsen U U

British journal of pharmacology 20140101 1

<h4>Background and purpose</h4>Hypoxia causes vasodilatation of coronary arteries, but the underlying mechanisms are poorly understood. We hypothesized that hypoxia reduces intracellular Ca(2+) concentration ([Ca(2+)](i)) by opening of K channels and release of H₂S.<h4>Experimental approach</h4>Porcine coronary arteries without endothelium were mounted for measurement of isometric tension and [Ca(2+)](i), and the expression of voltage-gated K channels K(V)7 channels (encoded by KCNQ genes) and l ...[more]

PMID: 24111896

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Dataset Information

KV 7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries.

Background and purpose

Experimental approach

Key results

Conclusion

Publications

KV 7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries.

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