Potentiating KCC2 activity is sufficient to limit the onset and severity of seizures

著者: Yvonne E. Moore, Tarek Z. Deeb, Heramb Chadchankar, Nicholas J. Brandon, Stephen J. Moss - Proceedings of the National Academy of Sciences, PNAS 2018 被引用: 114

extrusion, without altering total or plasma membrane accumulation of KCC2. Critically, activity-induced deficits in synaptic inhibition were reduced in the mutant mice. Consistent with this, enhanced KCC2 was sufficient to limit chemoconvulsant-induced epileptiform activity. Furthermore, this increase in KCC2 function mitigated induction of aberrant high-frequency activity during seizures, highlighting depolarizing GABA as a key contributor to the pathological neuronal synchronization seen in epilepsy. Thus, our results demonstrate that potentiating KCC2 represents a therapeutic strategy to alleviate seizures.