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 Ba2+. Because BaCl2 also blocks ATP-sensitive K+ channels (K-ATP) we challenged K+ dilations in penetrating, resistance-size (<60 m mu) rat neocortical vessels with the K-ATP channel blocker glibenclamide (1 mu M). 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 mu M) did not significantly change resting vessel diameter but decreased K+ dilations (from 153 +/- 9 to 99 +/- 2%). BaCl2 blocked K+ dilations with a half-maximal dissociation constant of 2.9 mu M 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.