Developmental changes in the physiology of GABAARs. GABAAR can normally elicit depolarising or hyperpolarising postsynaptic responses depending upon the electrochemical gradient of Cl-, between the intra- and extra-cellular space. In immature neurons, there are abundant cation chloride cotransporters that import Cl- (e.g. NKCC1) and scarce cation chloride cotransporters that export Cl- (e.g. KCC2), creating relatively high intracellular Cl- concentrations ([Cl-]i). As a result, opening of GABAARs leads to efflux of Cl-, depolarising these neurons. GABA depolarisations are necessary early in life as they support calcium-sensitive processes that are important for neuronal proliferation, migration, differentiation, and synaptic growth and integration. GABA depolarisations are not necessarily excitatory, as they do not necessarily trigger action potentials. In the face of excessive neuronal excitation (e.g. during seizures), the open GABAAR channels can still shunt excitatory currents, contributing a weak form of inhibition (shunting inhibition). In mature neurons, there is greater activity of KCC2 than NKCC1, which lowers [Cl-]i and permits the hyperpolarising GABAAR currents to emerge, once GABAARs open. This suggests that the efficacy of inhibitory effects of benzodiazepines may be enhanced in older age groups.