Effect of the Combination of NKCC1 and KCC2 Cotransporter Blockades on Non-synaptic Epileptiform Activities

摘要

Cation-chloride cotransporters (CCC's) have a direct effect on the regulation of intracellular chloride concentration ([Cl~-]i) and neuronal excitability. Several studies propose the blockade of CCC's as the main antiepileptic action of the diuretic furosemide (FUR). The aim of this study was to evaluate the effect of bumetanide (12.5 μM), VU0463271 (VU) (10 μM) and FUR (5 mM) cotrans-porter blockers on non-synaptic epileptiform activities (NEAs) by means of extracellular records in the dentate gyrus. Significant reduction in time between events occurred during infusion with the BUM, VU and BUM + VU inhibitors. Conversely, infusion with FUR promoted blockade of activities. Therefore, the blockade exerted by this diuretic does not result from its action on cotransporters.