Heterogeneity in Kv7 channel function in the cerebral and coronary circulation

Microcirculation. 2015 Feb;22(2):109-121. doi: 10.1111/micc.12183.


Objectives: Kv7 channels are considered important regulators of vascular smooth muscle contractility. The present study aimed to examine the hypotheses that (i) Kv7 channels are present in mouse cerebral and coronary arteries and regulate vascular reactivity and (ii) regional differences exist in the activity of these channels.

Methods and results: PCR confirmed that basilar, Circle of Willis and LAD arteries express predominantly Kv7.1 and 7.4. Western blot analysis, however, showed greater Kv7.4 protein levels in the cerebral vessels. Relaxation to the Kv7 channel activator, retigabine (1-50 μM) was significantly greater in the basilar artery compared to the LAD artery. Similarly, the Kv7 channel inhibitor, linopirdine (10 μM) caused a stronger contraction of the basilar artery. Furthermore, pre-incubation with linopirdine reduced forskolin (cAMP activator)-induced vasorelaxation in basilar while not altering forskolin-induced vasorelaxation of the LAD, suggesting that Kv7 channels play a more prominent role in the cerebral than in the coronary circulation. Consistent with the vessel data, whole cell Kv7 currents in cerebral VSMCs were potentiated by retigabine and inhibited by linopirdine, while these responses were blunted in coronary VSMCs.

Conclusions: This study provides evidence that mouse Kv7 channels may contribute differently to regulating the functional properties of cerebral and coronary arteries. Such heterogeneity has important implications for developing novel therapeutics for cardiovascular dysfunction.

Keywords: K+ channels; cerebral and coronary arteries; electrophysiology; pharmacological manipulation; regional heterogeneity; voltage-gated K+ channels.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basilar Artery / metabolism
  • Carbamates / pharmacology
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology*
  • Circle of Willis / metabolism
  • Colforsin / pharmacology
  • Coronary Circulation / drug effects
  • Coronary Circulation / physiology*
  • Indoles / pharmacology
  • KCNQ Potassium Channels / agonists
  • KCNQ Potassium Channels / antagonists & inhibitors
  • KCNQ Potassium Channels / genetics
  • KCNQ Potassium Channels / metabolism*
  • KCNQ1 Potassium Channel / agonists
  • KCNQ1 Potassium Channel / antagonists & inhibitors
  • KCNQ1 Potassium Channel / genetics
  • KCNQ1 Potassium Channel / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle, Smooth, Vascular / metabolism*
  • Organ Specificity / drug effects
  • Organ Specificity / physiology
  • Phenylenediamines / pharmacology
  • Potassium Channel Blockers / pharmacology
  • Pyridines / pharmacology
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology
  • Vasodilation / drug effects
  • Vasodilation / physiology
  • Vasodilator Agents / pharmacology


  • Carbamates
  • Indoles
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • Kcnq1 protein, mouse
  • Kcnq4 protein, mouse
  • Phenylenediamines
  • Potassium Channel Blockers
  • Pyridines
  • Vasodilator Agents
  • ezogabine
  • Colforsin
  • linopirdine