GABAA receptors (GABAARs) exist as different subtype variants showing unique functionalproperties and defined spatio-temporal expression pattern. The molecular mechanismsunderlying the developmental expression of different GABAAR are largely unknown. Theintracellular concentration of chloride ([Cl~-]i), the main ion permeating through GABAARs,also undergoes considerable changes during maturation, being higher at early neuronal stageswith respect to adult neurons. Here we investigate the possibility that [Cl~-]icould modulate the sequential expression of specific GABAARs subtypes in primary cerebellar neurons. We showthat [Cl~-]i regulates the expression of α3-1 and δ-containing GABAA receptors, responsible forphasic 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.
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