부산대학교 도서관

Background and Purpose Hypoxia causes vasodilatation of coronary arteries, but the underlying mechanisms are poorly understood. We hypothesized that hypoxia reduces intracellular Ca2+ concentration ([ Ca2+]i) by opening of K channels and release of H2S. Experimental Approach Porcine coronary arteries without endothelium were mounted for measurement of isometric tension and [ Ca2+]i, and the expression of voltage-gated K channels KV7 channels (encoded by KCNQ genes) and large-conductance calcium-activated K channels ( KCa1.1) was examined. Voltage clamp assessed the role of KV7 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 [ Ca2+]i in PGF 2α (10 μM)-contracted arteries whereas no fall in [ Ca2+]i was observed in 30 mM K-contracted arteries. Blockers of ATP-sensitive voltage-gated potassium channels and KCa1.1 inhibited hypoxia-induced dilatation in PGF2α-contracted arteries; this inhibition was more marked in the presence of the Kv7 channel blockers, XE991 and linopirdine, while a KV7.1 blocker, failed to change hypoxic vasodilatation. XE991 also inhibited H2S- and adenosine-induced vasodilatation. PCR revealed the expression of KV7.1, KV7.4, KV7.5 and KCa1.1 channels, and KCa1.1, KV7.4 and KV7.5 were also identified by immunoblotting. Voltage clamp studies showed the XE991-sensitive current was more marked in hypoxic conditions. Conclusion The KV7.4 and KV7.5 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 KV7 channels in this vasodilatation. Activation of these KV7 channels may be induced by H2S and adenosine. [ABSTRACT FROM AUTHOR]