The wild wide world of human GABAA receptors

Type-A gamma-aminobutyric receptors (GABAARs) are the principal mediators of rapid inhibitory synaptic transmission in the human brain. They form a large family of pentameric ligand-gated chloride channels, with a rich pharmacology and involved in virtually all aspects of brain function. Many GABAAR modulators, including benzodiazepines and general anaesthetics, are among the most successful drugs in clinical use (and often substances of abuse). I will discuss our journey towards the structural characterisation of human GABAARs and their vast molecular diversity. This work led to insights into the mechanisms of GABA-ergic signalling, a rational basis for the development of novel GABAAR modulators, and multiple unexpected findings that will keep us and others busy for the foreseeable future.