ABSTRACT
Controlling excitability in the brain is a vital aspect of our neurophysiology, the importance of which is exemplified by the many neurological diseases that are associated with dysfunction of brain inhibition. The major neurotransmitter signaling system responsible for maintaining control over neuronal excitability is focused on GABA and its associated receptors, type A (GABAA) and type B (GABAB). This chapter centers on the hetero-oligomeric GABAA receptor, discussing its key structural aspects, including the extracellular, transmembrane and intracellular modular-type domains. The life cycle of the receptor in the membrane is considered along with interactions with receptor-associated molecules, including protein kinases. With regard to functional aspects, important aspects related to receptor activation by GABA are described including modulation by a variety of ligands, incorporating details on their binding sites. These include molecules of experimental interest, such as agonists and antagonists, and also clinically relevant therapeutics, such as benzodiazepines, general anesthetics and neurosteroids. Overall, these many diverse features of the pentameric GABAA receptor serve to emphasize its important and widespread role in neurophysiology.
