Effect of potassium channel modulators on the release of glutamate induced by ischaemic-like conditions in rat hippocampal slices.
The effects of the potassium channel openers lemakalim, RP 52891 and galanin and the potassium channel blockers glibenclamide and gliquidone were evaluated by the release of endogenous glutamate from rat hippocampal slices subjected to a brief period of ischaemia (2-10 min). Ischaemia was mimicked by incubating slices in a glucose free medium equilibrated with 95% N2/5% CO2. These conditions evoked a release of glutamate which was insensitive to tetrodotoxin and Ca2+ indicating a non-vesicular origin. The release of glutamate evoked by a 6- or 8-min period of ischaemia was reduced by 25-40% in the presence of lemakalim (10 microM), RP 52891 (10 microM) or galanin (0.3 microM), whereas it was enhanced by 60 to 100% in the presence of glibenclamide (1 microM) and gliquidone (2 microM). These observations suggest that cellular damage resulting from ischaemia induced excessive release of glutamate in the hippocampus may be partly reduced by potassium channel openers, and conversely increased by sulfonylureas.
Zini
S
S
Laboratoire de Neurobiologie et Physiopathologie du Développement, INSERM U29, Paris, France.
Roisin
M P
MP
Armengaud
C
C
Ben-Ari
Y
Y
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D005947:Glucose / Q000502:physiology; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology
D005971:Glutamates; D015221:Potassium Channels; D018698:Glutamic Acid; D013779:Tetrodotoxin; D005947:Glucose