Intracellular chloride concentration influences the GABA A receptor subunit composition

GABA_A receptors (GABA_ARs) exist as different subtype variants showing unique functional properties and defined spatio-temporal expression pattern. The molecular mechanisms underlying the developmental expression of different GABA_AR are largely unknown. The intracellular concentration of chloride ([Cl^-]_i), the main ion permeating through GABA_ARs, also undergoes considerable changes during maturation, being higher at early neuronal stages with respect to adult neurons. Here we investigate the possibility that [Cl^-]_i could modulate the sequential expression of specific GABA_ARs subtypes in primary cerebellar neurons. We show that [Cl^-]_i regulates the expression of α3-1 and δ-containing GABA_A receptors, responsible for phasic and tonic inhibition, respectively. Our findings highlight the role of [Cl^-]_i in tuning the strength of GABAergic responses by acting as an intracellular messenger.