title: Potassium channel activators decrease endogenous glutamate release from rat cerebellar slices.
abstract: The effects of the sulphonylurea activators of ATP-sensitive potassium channels (K(+) ATP), cromakalim and pinacidil, on the evoked-release of endogenous glutamate from superfused slices of rat cerebellum was examined. K(+)-stimulated release was Ca(2+)-dependent, whereas tetrapentylammonium (TPeA)-evoked release occurred both in the presence and absence of Ca(2+), but was significantly greater in Ca(2+)-free medium. The Ca(2+)-dependent TPeA and K(+)-evoked release of glutamate was inhibited by both cromakalim and pinacidil in a concentration-dependent fashion. However, although cromakalim markedly reduced Ca(2+)-independent TPeA-evoked release, pinacidil was ineffective. In addition, the vehicle for cromakalim, ethanol, markedly potentiated both Ca(2+)-dependent and -independent TPeA-evoked release, but not K(+)-evoked release. Despite a high concentration of sulphonylurea binding sites and a dense glutamatergic innervation, the concentrations of K(+) ATP channel activators required to inhibit stimulus-evoked release from the cerebellum are higher than those reported to inhibit glutamate release or reduce neuronal activity in other parts of the CNS.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, CF4 4XN, Cardiff, UK.
authors.forename: B G
authors.initials: BG
authors.lastname: Dickie
authors.forename: J A
authors.initials: JA
authors.lastname: Davies