The cellular, molecular and ionic basis of GABAA receptor signalling

GABA(A) receptors mediate fast synaptic inhibition in the CNS. Whilst this is undoubtedly true, it is a gross oversimplification of their actions. The receptors themselves are diverse, being formed from a variety of subunits, each with a different temporal and spatial pattern of expression. This diversity is reflected in differences in subcellular targetting and in the subtleties of their response to GABA. While activation of the receptors leads to an inevitable increase in membrane conductance, the voltage response is dictated by the distribution of the permeant Cl- and HCO3- ions, which is established by anion transporters. Similar to GABA(A) receptors, the expression of these transporters is not only developmentally regulated but shows cell-specific and subcellular variation. Untangling all these complexities allows us to appreciate the variety of GABA-mediated signalling, a diverse set of phenomena encompassing both synaptic and non-synaptic functions that can be overtly excitatory as well as inhibitory.