AUTHOR=Lim Wee Meng , Chin Eunice W. M. , Tang Bor Luen , Chen Tingting , Goh Eyleen L. K. TITLE=WNK3 Maintains the GABAergic Inhibitory Tone, Synaptic Excitation and Neuronal Excitability via Regulation of KCC2 Cotransporter in Mature Neurons JOURNAL=Frontiers in Molecular Neuroscience VOLUME=14 YEAR=2021 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2021.762142 DOI=10.3389/fnmol.2021.762142 ISSN=1662-5099 ABSTRACT=
The activation of chloride (Cl−)permeable gamma (γ)-aminobutyric acid type A(GABAA) receptors induces synaptic inhibition in mature and excitation in immature neurons. This developmental “switch” in GABA function controlled by its polarity depends on the postnatal decrease in intraneuronal Cl− concentration mediated by KCC2, a member of cation-chloride cotransporters (CCCs). The serine-threonine kinase WNK3 (With No Lysine [K]), is a potent regulator of all CCCs and is expressed in neurons. Here, we characterized the functions of WNK3 and its role in GABAergic signaling in cultured embryonic day 18 (E18) hippocampal neurons. We observed a decrease in WNK3 expression as neurons mature. Knocking down of WNK3 significantly hyperpolarized