KV7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries
| Autor: | Hedegaard, E R, Nielsen, B D, Kun, A, Hughes, A D, Krøigaard, C, Mogensen, S, Matchkov, V V, Fröbert, O, Simonsen, U |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Adenosine
Time Factors Dose-Response Relationship Drug KCNQ Potassium Channels Swine Vasodilator Agents Research Papers Coronary Vessels Muscle Smooth Vascular Membrane Potentials Oxygen Vasodilation Potassium Channel Blockers Animals Calcium Signaling Hydrogen Sulfide Hypoxia Large-Conductance Calcium-Activated Potassium Channel alpha Subunits Signal Transduction |
| Popis: | 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.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.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 PGF2α -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.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 H₂S and adenosine. |
| Databáze: | OpenAIRE |
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