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.
During development there is a change in the expression of GABA A receptor subunits. Here, Succol and colleagues show that chloride ions mediate the change in α3-α1 and δ-containing GABA A receptors that mediate phasic and tonic inhibition, respectively.