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 microM 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 microM kainate. Inhibition of ligand-gated Cl(-) channels by 10 microM gabazine and 30 microM strychnine induced interictal activity (IA) that was only marginally affected by bumetanide. Removal of extracellular Mg(2+) induced both ILE and IA. Bumetanide had no effect on these ILE but enhanced the IA. Low-Mg(2+) solution containing 20 microM 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.
Institute of Physiology and Pathophysiology, Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany. wkilb@uni-mainz.de
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Sinning
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D000818:Animals; D000831:Animals, Newborn; D002034:Bumetanide / Q000494:pharmacology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D011188:Potassium / Q000494:pharmacology*; D028021:Sodium-Potassium-Chloride Symporters / Q000187:drug effects / Q000502:physiology; D064506:Solute Carrier Family 12, Member 2
D018118:Chloride Channels; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D008274:Magnesium; D011188:Potassium