We investigated the effect of bromide on gamma-aminobutyric acid (GABA)-activated currents in cultured cerebral neurons of the rat, employing whole-cell voltage- and current-clamp techniques. Application of 100 mu M GABA elicited currents whose reversal potential was 0 mV with equal concentrations of chloride in both pipette and bath solutions and more negative than -60 mV with 159 mM chloride extracellularly and 4 mM chloride inside. Bicuculline blocked the currents. These findings showed that the currents were composed of chloride flux through GABA(A) receptor-coupled channels. Reversal potential revealed a permeability ratio of bromide with respect to chloride (P-Br/P-Cl) of 1.51. When 100 mu M GABA was applied with the extracellular solution containing 140 mM bromide and 19 mM chloride, the currents were enhanced 2.00- and 1.91-fold at the holding potentials of -20 mV and 0 mV, respectively. Extracellular solutions containing various concentrations of bromide substituted for the same amount of chloride were applied with 100 mu M GABA. The therapeutic concentration of 10 mM and 20 mM bromide enhanced the currents 1.28- and 1.36-fold of the control currents at the holding potential of -20 mV, respectively. Under current-damp recording, a larger hyperpolarization was obtained by the application of GABA with a 140 mM bromide-containing solution. These findings suggest that bromide potentiated GABA-activated currents at the therapeutic concentrations ranging from 10 mM to 20 mM, causing the larger GABA-induced hyperpolarization. It is postulated that the antiepileptic effect of bromide might occur through the potentiation of inhibitory postsynaptic potentials elicited by GABA.
