EFFECT OF POTASSIUM CHANNEL MODULATORS ON THE RELEASE OF GLUTAMATE-INDUCED BY ISCHEMIC-LIKE CONDITIONS IN RAT HIPPOCAMPAL SLICES

The effects of the potassium channel openers lemakalim, RP 52891 and g alanin and the Potassium channel blockers glibenclamide and gliquidone were evaluated by the release of endogenous glutamate from rat hippoc ampal slices subjected to a brief period of ischaemia (2-10 min). Isch aemia was mimicked by incubating slices in a glucose free medium equil ibrated with 95% N2/5% CO2. These conditions evoked a release of gluta mate which was insensitive to tetrodotoxin and Ca2+ indicating a non-v esicular origin. The release of glutamate evoked by a 6- or 8-min peri od of ischaemia was reduced by 25-40% in the presence of lemakalim (10 muM), RP 52891 (10 muM) or galanin (0.3 muM), whereas it was enhanced by 60 to 100% in the presence of glibenclamide (1 muM) and gliquidone (2 muM). These observations suggest that cellular damage resulting fr om ischaemia induced excessive release of glutamate in the hippocampus may be partly reduced by potassium channel openers, and conversely in creased by sulfonylureas.