Intracellular chloride concentration influences the GABA A receptor subunit composition

Abstract

GABAA receptors (GABAARs) exist as different subtype variants showing unique functional properties and defined spatio-temporal expression pattern. The molecular mechanisms underlying the developmental expression of different GABAAR are largely unknown. The intracellular concentration of chloride ([Cl-]i), the main ion permeating through GABAARs, 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 GABAARs subtypes in primary cerebellar neurons. We show that [Cl-]i regulates the expression of α3-1 and δ-containing GABAA 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. © 2012 Macmillan Publishers Limited. All rights reserved.