GABA_A receptor dependent synaptic inhibition rapidly tunes KCC2 activity via the Cl^--sensitive WNK1 kinase.

ABSTRACT: The K⁺-Cl^- co-transporter KCC2 (SLC12A5) tunes the efficacy of GABA_A receptor-mediated transmission by regulating the intraneuronal chloride concentration [Cl^-]_i. KCC2 undergoes activity-dependent regulation in both physiological and pathological conditions. The regulation of KCC2 by synaptic excitation is well documented; however, whether the transporter is regulated by synaptic inhibition is unknown. Here we report a mechanism of KCC2 regulation by GABA_A receptor (GABA_AR)-mediated transmission in mature hippocampal neurons. Enhancing GABA_AR-mediated inhibition confines KCC2 to the plasma membrane, while antagonizing inhibition reduces KCC2 surface expression by increasing the lateral diffusion and end

SUBMITTER: Heubl M 

PROVIDER: S-EPMC5701213 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature