KV 7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries

Br J Pharmacol. 2014 Jan;171(1):69-82. doi: 10.1111/bph.12424.


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 H₂S.

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 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.

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 H₂S and adenosine.

Keywords: H2S; KV7; adenosine; calcium; coronary; hypoxia; potassium channels; vasodilatation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / pharmacology
  • Animals
  • Calcium Signaling
  • Coronary Vessels / metabolism
  • Coronary Vessels / physiopathology
  • Dose-Response Relationship, Drug
  • Hydrogen Sulfide / pharmacology
  • Hypoxia / genetics
  • Hypoxia / metabolism*
  • Hypoxia / physiopathology
  • KCNQ Potassium Channels / drug effects
  • KCNQ Potassium Channels / genetics
  • KCNQ Potassium Channels / metabolism*
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / metabolism
  • Membrane Potentials
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / physiopathology
  • Oxygen / metabolism*
  • Potassium Channel Blockers / pharmacology
  • Signal Transduction
  • Swine
  • Time Factors
  • Vasodilation* / drug effects
  • Vasodilator Agents / pharmacology


  • KCNQ Potassium Channels
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Potassium Channel Blockers
  • Vasodilator Agents
  • Adenosine
  • Oxygen
  • Hydrogen Sulfide