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. 2019 Feb 20;13:48. doi: 10.3389/fncel.2019.00048

Figure 4.

Figure 4

Regulation of KCC2 diffusion and membrane stability by GABAergic inhibition. The impact of inhibitory activity on KCC2 diffusion was explored while blocking neuronal activity and glutamate receptors activity with the Na+ channel blocker tetrodotoxin, the ionotropic glutamate receptor antagonist kynurenic acid, and the group I/group II mGluR antagonist R, S-MCPG. Chloride influx through GABAARs inhibits WNK1, leading to KCC2 dephosphorylation on threonines 906/1007 and membrane stabilization. Upon GABAAR blockade, reduced intracellular chloride activates WNK1 leading to KCC2 phosphorylation on threonines 906/1007 and increased KCC2 diffusion and subsequent internalization. From Heubl et al. (2017).