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

ABSTRACT: The type 2 K⁺/Cl^- cotransporter (KCC2) allows neurons to maintain low intracellular levels of Cl^-, a prerequisite for efficient synaptic inhibition. Reductions in KCC2 activity are evident in epilepsy; however, whether these deficits directly contribute to the underlying pathophysiology remains controversial. To address this issue, we created knock-in mice in which threonines 906 and 1007 within KCC2 have been mutated to alanines (KCC2-T906A/T1007A), which prevents its phospho-dependent inactivation. The respective mice appeared normal and did not show any overt phenotypes, and basal neuronal excitability was unaffected. KCC2-T906A/T1007A mice exhibited increased basal neuronal Cl^- extrusion, without altering total or plasma membrane accumulation

SUBMITTER: Moore YE 

PROVIDER: S-EPMC6176565 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature