POTASSIUM CHANNEL ACTIVATORS DECREASE ENDOGENOUS GLUTAMATE RELEASE FROM RAT CEREBELLAR SLICES

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 Ca2+-dependent, whereas tetrapentylammonium (TPeA)-evoked release occurred both in the presence and absence of Ca2+, but was significantly greater in Ca2+-free medium. The Ca2+-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 Ca2+-independent TPeA-evoked release, pinacidil was ineffective. In addition, the vehicle for cromakalim, ethanol, markedly potentiated both Ca2+-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.