Model-specific effects of bumetanide on epileptiform activity in the in-vitro intact hippocampus of the newborn mouse

The immature brain has a higher susceptibility to develop seizures, which often respond poorly to classical pharmacological treatment. It has been recently suggested that bumetanide, which blocks Na+-dependent K+-Cl--cotransporter isoform 1 (NKCC1) and thus attenuates depolarizing GABAergic responses, could soothe epileptiform activity in immature nervous systems. To evaluate whether bumetanide consistently attenuates epileptiform activity, we investigated the effect of 10 mu M bumetanide in five different in-vitro epilepsy models using field potential recordings in the CA3 region of intact mouse hippocampal preparations at postnatal day 4-7. Bumetanide reduced amplitude and frequency of ictal-like events (ILE) induced by 8.5 mM K+, but it increased the frequency of ILE induced by 1 mu M kainate. Inhibition of ligand-gated Cl- channels by 10 mu M gabazine and 30 mu M strychnine induced interictal activity (IA) that was only marginally affected by bumetanide. Removal of extracellular Mg2+ induced both ILE and IA. Bumetanide had no effect on these ILE but enhanced the IA. Low-Mg2+ solution containing 20 mu M 4-AP induced late-recurrent discharges, which were slightly attenuated by bumetanide. In summary, our results demonstrate that bumetanide exerts diverse effects in different in-vitro epilepsy models. (C) 2007 Elsevier Ltd. All rights reserved.