BROMIDE, IN THE THERAPEUTIC CONCENTRATION, ENHANCES GABA-ACTIVATED CURRENTS IN CULTURED NEURONS OF RAT CEREBRAL-CORTEX

We investigated the effect of bromide on gamma-aminobutyric acid (GABA )-activated currents in cultured cerebral neurons of the rat, employin g whole-cell voltage- and current-clamp techniques. Application of 100 mu M GABA elicited currents whose reversal potential was 0 mV with eq ual concentrations of chloride in both pipette and bath solutions and more negative than -60 mV with 159 mM chloride extracellularly and 4 m M chloride inside. Bicuculline blocked the currents. These findings sh owed 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 10 0 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. E xtracellular solutions containing various concentrations of bromide su bstituted for the same amount of chloride were applied with 100 mu M G ABA. 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 holdi ng 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 brom ide potentiated GABA-activated currents at the therapeutic concentrati ons ranging from 10 mM to 20 mM, causing the larger GABA-induced hyper polarization. It is postulated that the antiepileptic effect of bromid e might occur through the potentiation of inhibitory postsynaptic pote ntials elicited by GABA.