Effect of a gamma-aminobutyric acid uptake inhibitor, NNC-711, on spontaneous postsynaptic currents in cultured rat hippocampal neurons: implications for antiepileptic drug development.

Abstract

The effect of a novel gamma-aminobutyric acid (GABA) uptake inhibitor, NNC-711, on spontaneous postsynaptic currents was studied in cultured rat hippocampal neurons by the whole cell patch clamp method. NNC-711 decreased the amplitude of inhibitory postsynaptic currents (IPSCs) and did not prolong the decay. NNC-711 also decreased the amplitude of excitatory PSCs (EPSCs). The GABAB receptor antagonist 2-OH saclofen abolished the effect on both IPSCs and EPSCs. NNC-711 itself induced no current and had no effect on currents induced by exogenously applied GABA. These findings suggest that duration of GABAA-receptor mediated IPSCs is not determined by GABA uptake and that GABA uptake inhibitors may work by allowing GABA to remain in the synaptic area long enough to activate presynaptic GABAB receptors.