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, employing whole-cell voltage- and current-clamp techniques. Application of 100 microM 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 GABAA receptor-coupled channels. Reversal potential revealed a permeability ratio of bromide with respect to chloride (PBr/PCl) of 1.51. When 100 microM 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 microM 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-clamp 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.
Suzuki
S
S
National Epilepsy Center, Shizuoka Higashi Hospital, Japan.
Kawakami
K
K
Nakamura
F
F
Nishimura
S
S
Yagi
K
K
Seino
M
M
D000818:Animals; D001965:Bromides / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D004553:Electric Conductivity; D004594:Electrophysiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001965:Bromides; D005680:gamma-Aminobutyric Acid