Model-specific effects of bumetanide on epileptiform activity in the in-vitro intact hippocampus of the newborn mouse
W Kilb, A Sinning, HJ Luhmann - Neuropharmacology, 2007 - Elsevier
W Kilb, A Sinning, HJ Luhmann
Neuropharmacology, 2007•ElsevierThe 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 10μM bumetanide in five different in-vitro …
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 10μM bumetanide in five different in-vitro …
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 10μM 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 8.5mM K+, but it increased the frequency of ILE induced by 1μM kainate. Inhibition of ligand-gated Cl− channels by 10μM gabazine and 30μM 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 20μM 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.
Elsevier
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