Quisqualic acid induced sensitization and the active uptake of l-quisqualic acid by hippocampal slices

Hippocampal CA1 pyramidal cell neurons are sensitized to depolarization by l-2-amino-4-phosphonobutanoic acid (l-AP4) following exposure to l-quisqualic acid (QUIS). It has been proposed that induction of this 'QUIS-effect' involves uptake of l-QUIS by hippocampal cells. We have used o-phthaldialdehyde (OPA) derivatization and high performance liquid chromatographic (HPLC) separation of extracts from hippocampal slices which have been exposed to varied concentrations of l-QUIS to investigate l-QUIS uptake into hippocampal slices. We observe uptake rates such that the internal concentration of l-QUIS exceeds the bath concentration within 7 min. The fact that this uptake is concentrative indicates that it is mediated by an active transport system. In addition, uptake of l-QUIS may be linked to the induction of the QUIS-effect. At low concentrations of l-QUIS (< 4 μM), the QUIS-effect is only partially induced within the 4 min incubation time which maximally induces the effect when 16 μM l-QUIS is used. However, repeated 4 min exposure periods of slices to low l-QUIS concentrations will eventually induce the QUIS-effect even when each exposure is separated by extensive washout periods. Hence induction is dependent on both concentration and total exposure time. We also examined the effects of l-α-aminoadipic acid and l-serine-O-sulfate on the rate of l-QUIS uptake. Exposure of slices to these compounds prior to treatment with l-QUIS will block the physiological effects of l-QUIS. We found that these 'pre-blocking' compound did not decrease the rate of l-QUIS uptake. However, like l-QUIS, these compounds undergo uptake and exert their effects in a manner which is dependent on both concentration and total exposure time.