Chloride transporters and GABA polarity in developmental, neurological and psychiatric conditions

Neuronal chloride regulation is a determinant factor for the dynamic tuning of GABAergic inhibition during and beyond brain development. This regulation is mainly dependent on the two co-transporters K ⁺ /Cl ⁻ co-transporter KCC2 and Na ⁺ /K ⁺ /Cl ⁻ co-transporter NKCC1, whose activity can decrease or increase neuronal chloride concentrations respectively. Altered expression and/or activity of either of these co-transporters has been associated with a wide variety of brain disorders including developmental disorders, epilepsy, schizophrenia and stroke. Here, we review current knowledge on chloride transporter expression and activity regulation and highlight the intriguing potential for existing and future interventions to support chloride homeostasis across a wide range of mental disorders and neurological conditions.