Reverse transport of glutamate during depolarization in immature hippocampal slices

Abstract

We studied the source of extracellular glutamate released by hippocampal slices obtained from P14 or adult rats, during 50 mM K + depolarization by using two potent inhibitors of Na +-dependent glutamate transport: l- trans-pyrrolidine-2,4-dicarboxylate (PDC), which is a relatively non-selective inhibitor of various glutamate transporter subtypes and dihydrokainic acid (DHK), a specific inhibitor of the glial transporter, GLT-1. Most depolarization-induced glutamate release was Ca 2+-dependent in adults, while in P14 slices most glutamate release was Ca 2+-independent. PDC decreased depolarization-induced glutamate release in P14 slices but not in adults. DHK increased glutamate release in adults but not in P14 slices. These data suggest that most depolarization-induced glutamate release in immature hippocampal slices is due to reversal of transport through a PDC-sensitive Na +-dependent glutamate transporter, presumably acting on presynaptic or cytoplasmic neuronal pools, and is not due to exocytosis from vesicular pools.