title: Diphenyl phosphine oxide-1-sensitive K(+) channels contribute to the vascular tone and reactivity of resistance arteries from brain and skeletal muscle.
abstract: OBJECTIVE
  Many types of vascular smooth muscle cells exhibit prominent KDR currents. These KDR currents may be mediated, at least in part, by KV1.5 channels, which are sensitive to inhibition by DPO-1. We tested the hypothesis that DPO-1-sensitive KDR channels regulate the tone and reactivity of resistance-sized vessels from rat brain (MCA) and skeletal muscle (GA).
  
  
  METHODS
  Middle cerebral and gracilis arteries were isolated and subjected to three kinds of experimental analysis: (i) western blot/immunocytochemistry; (ii) patch clamp electrophysiology; and (iii) pressure myography.
  
  
  RESULTS
  Western blot and immunocytochemistry experiments demonstrated KV1.5 immunoreactivity in arteries and smooth muscle cells isolated from them. Whole-cell patch clamp experiments revealed smooth muscle cells from resistance-sized arteries to possess a KDR current that was blocked by DPO-1. Resistance arteries constricted in response to increasing concentrations of DPO-1. DPO-1 enhanced constrictions to PE and serotonin in gracilis and middle cerebral arteries, respectively. When examining the myogenic response, we found that DPO-1 reduced the diameter at any given pressure. Dilations in response to ACh and SNP were reduced by DPO-1.
  
  
  CONCLUSIONS
  We suggest that KV1.5, a DPO-1-sensitive KDR channel, plays a major role in determining microvascular tone and the response to vasoconstrictors and vasodilators.
authors: Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, West Virginia, USA.
authors: Ibra S
authors: IS
authors: Fancher
authors: Joshua T
authors: JT
authors: Butcher
authors: Steven D
authors: SD
authors: Brooks
authors: Trey S
authors: TS
authors: Rottgen
authors: Paulina R
authors: PR
authors: Skaff
authors: Jefferson C
authors: JC
authors: Frisbee
authors: Gregory M
authors: GM
authors: Dick
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply*; D051666:Kv1.5 Potassium Channel / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020768:Middle Cerebral Artery / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
chemical_list: C496982:Kcna5 protein, mouse; C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D009943:Organophosphorus Compounds; C063888:triphenylphosphine oxide
keywords: KCNA5; KV1.5; delayed rectifier potassium current; diphenyl phosphine oxide-1; smooth muscle