Sodium bromide: effects on different patterns of epileptiform activity, extracellular pH changes and GABAergic inhibition

Results regarding the anticonvulsant potency of bromide have been questione d, and the mechanisms of its action are unclear. Using combined rat hippoca mpus entorhinal cortex slices we analyzed the effects of NaBr on four types of epileptiform discharges in two different models of epilepsy, the low-Ca 2+ and the low-Mg2+ model. NaBr concentration-dependently reduced the frequ ency and finally blocked the low Ca2+-induced discharges. Low Mg2+-induced short recurrent discharges were also reduced in a concentration-dependent m anner. In the entorhinal cortex the frequency of seizure-like events was re duced by 3 and 5 mM and the discharges were blocked by 7 mM NaBr. Also, the late recurrent discharges in the entorhinal cortex which do not respond to most clinically employed anticonvulsants were reduced by concentrations of 10 and 15 mM and completely blocked by 30 mM NaBr. Using pH-sensitive microelectrodes different effects of NaBr were seen than those of acetazolamide on extracellular pH under control conditions and af ter stimulation. Acetazolamide at 1 mM caused a reversible acidification of Delta pH: 0.2+/-0.14 at rest whereas no change on extracellular pH was see n with 5 mM NaBr. Acetazolamide increased the transient alkalosis induced b y repetitive stimulation of the stratum radiatum in area CAI and reduced th e subsequent acidosis. NaBr also increased the alkalosis but had no effect on the subsequent acidosis. A significant increase in paired-pulse inhibition was seen in a paired-puls e stimulation protocol used to monitor the efficacy of GABAergic inhibition at concentrations of 5 mM NaBr. This finding was confirmed in whole-cell p atch clamp recordings from cultured hippocampal neurons showing an increase in inhibitory postsynaptic current amplitude. In summary, our results suggest a broad-spectrum anticonvulsant activity wh ich is likely to be caused by its effects on membrane excitability, by an i ncrease in GABAergic inhibition and is less likely caused by its effects on extracellular pH.