KCC2 activity is critical in limiting the onset and severity of status epilepticus

摘要: The K+/Cl– cotransporter (KCC2) allows adult neurons to maintain low intracellular Cl– levels, which are a prerequisite for efficient synaptic inhibition upon activation of γ-aminobutyric acid receptors. Deficits in KCC2 activity implicated epileptogenesis, but how increased neuronal leads transporter inactivation is ill defined. In vitro, the potentiated via phosphorylation serine 940 (S940). Here we have examined role this putative regulatory process plays determining during status epilepticus (SE) using knockin mice S940 mutated an alanine (S940A). wild-type mice, SE induced by kainate resulted dephosphorylation and internalization. S940A homozygotes were viable exhibited comparable basal levels expression relative WT mice. However, exposure lethality within 30 min injection subsequent entrance into SE. We assessed effect mutation cultured hippocampal explore mechanisms underlying phenotype. Under conditions, had no on extrusion. selective deficit was seen transient glutamate. Significantly, whereas effects glutamate function could be ameliorated with agents that enhance phosphorylation, positive modulation lost neurons. Collectively our results suggest critical potentiating limit development