ATP-sensitive potassium channels may participate in the coupling of neuronal activity and cerebrovascular tone.
K(+) dilate and constrict cerebral vessels in a dose-dependent fashion. Modest elevations of abluminal K(+) cause vasodilatation, whereas larger extracellular K(+) concentration ([K(+)](out)) changes decrease cerebral blood flow. These dilations are believed to be mediated by opening of inward-rectifier potassium channels sensitive to Ba(2+). Because BaCl(2) also blocks ATP-sensitive K(+) channels (K(ATP)), we challenged K(+) dilations in penetrating, resistance-size (<60 mmu) rat neocortical vessels with the K(ATP) channel blocker glibenclamide (1 microM). Glibenclamide reduced K(+) responses from 138 +/- 8 to 110 +/- 0.8%. K(+) constrictions were not affected by glibenclamide. The Na(+)-K(+)-pump inhibitor ouabain (200 microM) did not significantly change resting vessel diameter but decreased K(+) dilations (from 153 +/- 9 to 99 +/- 2%). BaCl(2) blocked K(+) dilations with a half-maximal dissociation constant of 2.9 microM and reduced dilations to the specific K(ATP) agonist pinacidil with equal potency. We conclude that, in resistance vessels, K(+) dilations are mediated by K(ATP); we hypothesize that [K(+)](out) causes activation of Na(+)-K(+) pumps, depletion of intracellular ATP concentration, and subsequent opening of K(ATP). This latter hypothesis is supported by the blocking effect of ouabain.
Nguyen
T S
TS
Departments of Neurological Surgery, Harborview Medical Center, University of Washington, Seattle, Washington 98104, USA.
Winn
H R
HR
Janigro
D
D
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D001921:Brain / Q000098:blood supply*; D002712:Chlorides / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006868:Hydrolysis; D007700:Kinetics; D019579:Neocortex / Q000098:blood supply; D009474:Neurons / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D017609:Barium Compounds; D002712:Chlorides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C024986:barium chloride; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D005905:Glyburide