title: Heterogeneity in Kv7 channel function in the cerebral and coronary circulation.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri-Columbia, MO 65211.
authors.forename: Sewon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri-Columbia, MO 65211.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri-Columbia, MO 65211.
authors.forename: Miles A
authors.initials: MA
authors.lastname: Tanner
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri-Columbia, MO 65211.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri-Columbia, MO 65211.|Department of Medical Pharmacology & Physiology, University of Missouri-Columbia, MO 65211.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hill
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000378:metabolism; D002219:Carbamates / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D002941:Circle of Willis / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D051656:KCNQ Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051657:KCNQ1 Potassium Channel / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009928:Organ Specificity / Q000187:drug effects / Q000502:physiology; D010655:Phenylenediamines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002219:Carbamates; D007211:Indoles; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496910:Kcnq1 protein, mouse; C492167:Kcnq4 protein, mouse; D010655:Phenylenediamines; D026902:Potassium Channel Blockers; D011725:Pyridines; D014665:Vasodilator Agents; C101866:ezogabine; D005576:Colforsin; C061017:linopirdine
keywords: K+ channels; cerebral and coronary arteries; electrophysiology; pharmacological manipulation; regional heterogeneity; voltage-gated K+ channels