title: Molecular mechanisms of the inhibitory effects of clonidine on vascular adenosine triphosphate-sensitive potassium channels.
abstract: BACKGROUND
  We investigated the effects of the imidazoline-derived α2-adrenoceptor agonist clonidine on vascular adenosine triphosphate-sensitive potassium (K(ATP)) channel activity in rat vascular smooth muscle cells and recombinant vascular K(ATP) channels transiently expressed in COS-7 cells.
  
  
  METHODS
  Using the patch-clamp method, we investigated the effects of clonidine on the following: (1) native vascular K(ATP) channels; (2) recombinant K(ATP) channels with different combinations of various types of inwardly rectifying potassium channel (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor (SUR1, 2A, 2B) subunits; (3) SUR-deficient channels derived from a truncated isoform of the Kir6.2 subunit (Kir6.2ΔC36 channels); and (4) mutant Kir6.2ΔC36 channels with diminished sensitivity to ATP (Kir6.2ΔC36-K185Q channels).
  
  
  RESULTS
  Clonidine (≥3 × 10(-8) M) inhibited native K(ATP) channel activity in cell-attached configurations with a half-maximal inhibitory concentration value of 1.21 × 10(-6) M and in inside-out configurations with a half-maximal inhibitory concentration value of 0.89 × 10(-6) M. With similar potency, clonidine (10(-6) or 10(-3) M) also inhibited the activities of various recombinant SUR/Kir6.0 K(ATP) channels, the Kir6.2ΔC36 channel, and the Kir6.2ΔC36-K185Q channel.
  
  
  CONCLUSIONS
  Clinically relevant concentrations of clonidine inhibit K(ATP) channel activity in vascular smooth muscle cells. This inhibition seems to be the result of its effect on the Kir6.0 subunit and not on the SUR subunit.
authors: Department of Anesthesiology, Tokushima University Hospital, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. kawahito@pb4.so-net.ne.jp
authors: Shinji
authors: S
authors: Kawahito
authors: Takashi
authors: T
authors: Kawano
authors: Hiroshi
authors: H
authors: Kitahata
authors: Jun
authors: J
authors: Oto
authors: Akira
authors: A
authors: Takahashi
authors: Kazumi
authors: K
authors: Takaishi
authors: Nagakatsu
authors: N
authors: Harada
authors: Tadahiko
authors: T
authors: Nakagawa
authors: Hiroyuki
authors: H
authors: Kinoshita
authors: Toshiharu
authors: T
authors: Azma
authors: Yutaka
authors: Y
authors: Nakaya
authors: Shuzo
authors: S
authors: Oshita
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003000:Clonidine / Q000494:pharmacology*; D006801:Humans; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000502:physiology*; D051381:Rats; D000099161:Kcnj11 Channel
chemical_list: D003000:Clonidine; D054086:KATP Channels; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel