In the CNS, γ-aminobutyric acid (GABA) acts as an inhibitory transmitter via ligand-gated GABAA receptor channels and G protein-coupled GABAB receptors. Both of these receptor types mediate inhibitory postsynaptic transmission throughout the nervous system. For GABAA receptors, this inhibitory action is associated with a hyperpolarization due to an increase in conductance to chloride ions. Previous studies show that GABAA receptor activation in neonatal neurons and spinal cord neurons can be excitatory. Two papers recently appeared that clearly demonstrate that GABA can have a depolarizing and excitatory action in mature cortical neurons. Here we discuss the evolving story on chloride ion homeostasis in CNS neurons and its role in the bipolar life of the GABAA receptor.
