Glutamine-induced membrane currents in cultured rat hippocampal neurons

Glutamine is present at high concentrations in the extracellular fluid of the brain. It shuttles between glia cells and neurons, and serves as a precursor for both glutamate and gamma-amino butyric acid. Direct actions of glutamine at central neurons are, however, not well understood. Here we showed that L-glutamine (0.5-10 mM) evoked a dose-dependent inward transmembrane current in primarily cultured rat hippocampal neurons. Typical responses were outwardly rectifying and had a reversal potential around 0 mV. The current was partially sensitive towards blockers of ionotropic glutamate receptors and was partially carried by activation of N-methyl-D-aspartate receptors. However, cellular responses to L-glutamine showed clear biophysical and pharmacological differences to L-glutamate-evoked currents. Responses were highly specific for L-glutamine and no responses could be evoked by D-glutamine, L-alanine, L-valine, L-leucine and the system-A-specific agonist alpha-(methylamino)-isobutyric acid. Together, these data indicate that hippocampal neurons can be depolarized by electrogenic effects specific for L-glutamine.