GABA

GABA activates GABA-A and GABA-B receptors and primarily reduces neuronal excitability in the mature mammalian central nervous system.⁶ At GABA-A receptors, it opens chloride channels⁷; the direction of chloride movement determines whether its action is hyperpolarizing, depolarizing, or shunting, with shunting reducing the influence of other incoming signals. At GABA-B receptors, it regulates ion channels through G proteins and can also produce excitatory effects through activation of voltage-dependent calcium channels. GABA supports both rapid synaptic inhibition and slower tonic inhibition, while its effects in immature neurons can be excitatory because their chloride gradients differ.

GABA also regulates neural progenitor proliferation, migration, differentiation, and synapse formation, and GABA-A receptor activation can limit cell growth by arresting the cell cycle. In pancreatic islets, GABA inhibits glucagon secretion and can promote beta-cell replication and survival and the conversion of alpha cells to beta cells. It can suppress inflammatory immune responses and promote regulatory responses, with inhibition of autoimmune disease reported in several animal models. In rats, GABA enhances serotonin conversion toward a melatonin precursor, suggesting a possible role in melatonin synthesis.