title: Smooth muscle Ca(2+) -activated and voltage-gated K+ channels modulate conducted dilation in rat isolated small mesenteric arteries.
abstract: OBJECTIVE
  To assess the influence of blocking smooth muscle large conductance Ca(2+) -activated K+ channels and voltage-gated K+ channels on the conducted dilation to ACh and isoproterenol.
  
  
  METHODS
  Rat mesenteric arteries were isolated with a bifurcation, triple-cannulated, pressurized and imaged using confocal microscopy. Phenylephrine was added to the superfusate to generate tone, and agonists perfused into a sidebranch to evoke local dilation and subsequent conducted dilation into the feed artery.
  
  
  RESULTS
  Both ACh- and isoproterenol-stimulated local and conducted dilation with similar magnitudes of decay with distance along the feed artery (2000μm: ∼15% maximum dilation). The gap junction uncoupler carbenoxolone prevented both conducted dilation and intercellular spread of dye through gap junctions. IbTx, TEA or 4-AP, blockers of large conductance Ca(2+) -activated K+ channels and voltage-gated K+ channels, did not affect conducted dilation to either agonist. A combination of either IbTx or TEA with 4-AP markedly improved the extent of conducted dilation to both agonists (2000μm: >50% maximum dilation). The enhanced conducted dilation was reflected in the hyperpolarization to ACh (2000μm: Control, 4±1 mV, n = 3; TEA with 4-AP, 14±3mV, n=4), and was dependent on the endothelium.
  
  
  CONCLUSIONS
  These data show that activated BK(Ca) and K(V) -channels serve to reduce the effectiveness of conducted dilation.
authors.affiliation: Department of Pharmacology, University of Oxford, Oxford, UK Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
authors.forename: Timea Z
authors.initials: TZ
authors.lastname: Beleznai
authors.forename: Polina L
authors.initials: PL
authors.lastname: Yarova
authors.forename: Kathryn H
authors.initials: KH
authors.lastname: Yuill
authors.forename: Kim A
authors.initials: KA
authors.lastname: Dora
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D017629:Gap Junctions / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D014665:Vasodilator Agents; D007545:Isoproterenol; D000109:Acetylcholine