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K V 7 channels are involved in hypoxia‐induced vasodilatation of porcine coronary arteries
Author(s) -
Hedegaard E R,
Nielsen B D,
Kun A,
Hughes A D,
Krøigaard C,
Mogensen S,
Matchkov V V,
Fröbert O,
Simonsen U
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12424
Subject(s) - vasodilation , coronary arteries , hypoxia (environmental) , medicine , chemistry , potassium channel , channel blocker , charybdotoxin , contraction (grammar) , patch clamp , endocrinology , cardiology , calcium , artery , electrophysiology , oxygen , organic chemistry
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 2 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 2α (10 μM)‐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 PGF 2α ‐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 2 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 2 S and adenosine.