Blockade of GABA Transporter (GAT-1) Modulates the GABAergic Transmission in the Rat Globus Pallidus

Previous studies from our laboratory have demonstrated that application of SKF 89976A, a selective inhibitor of the GABA transporter GAT 1, reduces the activity of pallidal neurons in monkeys. However, the functional role of GAT 1 on GABAergic synaptic transmission in the globus pallidus (GP) is poorly understood. In the present study, we applied the whole-cell patch clamp recording technique to study the effects of blockade of GAT 1 on GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) recorded from rat GP slice preparations. Under maximal striatal stimulation (15-20V) in parasagittal slices, SKF 89976A (10 mu M) significantly prolonged the decay time, without significant effect on the amplitude, of IPSC. In contrast, SKF 89976A increased the amplitude, but did not prolong the decay time, of IPSCs under minimal striatal stimulation (2-5 V). We did not find any significant effect of SKF 89976A on IPSCs evoked locally from GP coronal slices. Furthermore, neither the amplitude nor the frequency of miniature IPSCs were changed following bath application of SKF 89976A. These results demonstrate that GABA reuptake through GAT-1 plays a major activity-dependent role in regulating GABAergic transmission at striatopallidal synapses in the GP.