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KV7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries

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  • Elise Nielsen
  • ,
  • Berit Dalsgaard Nielsen
  • Attila Kun
  • ,
  • Alun Hughes, Imperial College London, Department of Clinical Pharmacology, St. Mary's Hospital, University College London, International Centre for Circulatory Health, National Heart and Lung Institute Division, Faculty of Medicine, Imperial College London, Dept. of Clin. Pharmacology, Imperial Coll., London, United Kingdom
  • Christel Krøigaard
  • ,
  • Susie Mogensen
  • Vladimir Matchkov
  • Ole Frøbert
  • Ulf Simonsen
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 H2 S. Porcine coronary arteries without endothelium were mounted for measurement of isometric tension and [Ca(2+) ]i , and the expression of voltage-gated K channels (KV ) subtype 7 (KV 7 channels encoded by KCNQ genes) and large-conductance calcium-activated K channels (BKCa ) was examined. Voltage clamp assessed the role of KV 7 channels in hypoxia. Gradual reduction of oxygen concentration from 95% to 1% dilated the coronary arteries and was associated with reduced [Ca(2+) ]i in prostaglandin F2α (PGF2α 10 μM)-contracted arteries whereas no fall in [Ca(2+) ]i was observed in 30 mM K-contracted arteries. Blockers of ATP-sensitive and voltage-gated potassium channels, and BKCa inhibited hypoxia-induced dilatation in PGF2α -contracted arteries; the inhibition was most pronounced in the presence of the Kv7 channel blockers, XE991 and linopirdine, while a KV 7.1 blocker, failed to change hypoxic vasodilatation. XE991 also inhibited H2 S- and adenosine-induced vasodilatation. PCR revealed expression of KV 7.1, KV 7.4, KV 7.5, and BKCa channels, and BKCa , KV 7.4 and KV 7.5 was also found by immunoblotting. Voltage clamp studies showed a more pronounced XE991-sensitive current in hypoxic conditions. The KV 7.4 and KV 7.5 channels, which we identified in the coronary arteries, appear to be a main component in the hypoxia-induced vasodilatation. Voltage clamp results further support a role for KV 7 channels during hypoxia. H2 S and adenosine may also lead to the activation of KV 7 channels.
Original languageEnglish
JournalBritish Journal of Pharmacology
Publication statusPublished - 1 Sep 2013

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