Blockade of GABA uptake potentiates GABA-induced depolarizations in adult mouse cortical slices

Abstract

The electrophysiological effects of GABA and the GABA uptake inhibitor, NO-711, were investigated on cortical slices prepared from adult audiogenic seizure-prone DBA/2 mice. GABA, perfused for 1 min, elicited depolarizing responses which had a mean duration of 80-100 s and were concentration-dependent (0.1-32 mM). NO-711 (25 microM), perfused for 15 min, produced depolarizations with a mean duration of 50-60 s and these persisted for 4-5 h. The responses to both compounds were blocked by the GABA(A) receptor antagonist, bicuculline. Pre-treatment of the slices with NO-711 potentiated the responses to GABA and moved the concentration-response curve to the left. The EC50 to GABA following pre-treatment with NO-711 was 111+/-24 microM from a control value of 1.17+/-0.19 mM. These results demonstrate that in cortical slices GABA has a depolarizing action rather than the conventional one of hyperpolarization and that this response is potentiated by inhibition of GABA reuptake.