TY - JOUR

T1 - KV7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries

AU - Nielsen, Elise

AU - Nielsen, Berit Dalsgaard

AU - Kun, Attila

AU - Hughes, Alun

AU - Krøigaard, Christel

AU - Mogensen, Susie

AU - Matchkov, Vladimir

AU - Frøbert, Ole

AU - Simonsen, Ulf

PY - 2013/9/1

Y1 - 2013/9/1

N2 - 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.

AB - 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.

M3 - Journal article

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

ER -