title: Dexmedetomidine directly inhibits vascular ATP-sensitive potassium channels.
abstract: OBJECTIVE
  Dexmedetomidine is reported to have an effect on peripheral vasoconstriction; however, the exact mechanisms underlying this process are unclear. In this study, we hypothesized that dexmedetomidine-induced inhibition of vascular ATP-sensitive K(+) (K(ATP)) channels may be associated with this vasoconstriction. To test this hypothesis, we investigated the effects of dexmedetomidine on vascular K(ATP)-channel activity at the single-channel level.
  
  
  METHODS
  We used cell-attached and inside-out patch-clamp configurations to examine the effects of dexmedetomidine on the activities of native rat vascular K(ATP) channels, recombinant K(ATP) channels with different combinations of various inwardly rectifying potassium channels (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor subunits (SUR1, 2A, 2B), and SUR-deficient channels derived from a truncated isoform of Kir6.2 subunit, namely, Kir6.2ΔC36 channels.
  
  
  RESULTS
  Dexmedetomidine was observed to inhibit the native rat vascular K(ATP) channels in both cell-attached and inside-out configurations. This drug also inhibited the activity of all types of recombinant SUR/Kir6.0 K(ATP) channels as well as Kir6.2ΔC36 channels with equivalent potency.
  
  
  CONCLUSIONS
  These results indicate that dexmedetomidine directly inhibits K(ATP) channels through the Kir6.0 subunit.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Kochi Medical School, Kochi, Japan. takashika@kochi-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawano
authors.forename: Fumimoto
authors.initials: F
authors.lastname: Yamazaki
authors.forename: Haidong
authors.initials: H
authors.lastname: Chi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kawahito
authors.forename: Satoru
authors.initials: S
authors.lastname: Eguchi
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D020927:Dexmedetomidine / Q000494:pharmacology*; D054086:KATP Channels / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D054086:KATP Channels; D011994:Recombinant Proteins; D020927:Dexmedetomidine