Molecular Biology and Ontogeny of γ-Aminobutyric Acid (GABA) Receptors in the Mammalian Central Nervous System

Abstract

γ-Aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the mammalian central nervous system. After release from nerve terminals, GABA binds to at least two classes of postsynaptic receptors (ie, GABA_A and GABA_B), which are nearly ubiquitous in the brain. GABA_A receptors are postsynaptic heteropentameric complexes that display unique physiologic and pharmacologic properties based on subunit composition. Activation of GABA_A receptors in mature neurons results in membrane hyperpolarization, which is mediated principally by inward chloride flux, whereas in early stages of brain development, GABA_A receptor activation causes depolarization of the postsynaptic membrane. GABA_B receptors reside both presynaptically and postsynaptically, exist as heterodimers and are coupled to voltage-dependent ion channels through interactions with heterotrimeric G proteins. This review summarizes the molecular biology and ontogeny of GABA_A and GABA_B receptors, highlighting some of their putative roles during normal brain development as well as in disease states such as epilepsy. (J Child Neurol 2003; 18: 39—48).

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