Diversity of structure and function of GABA_B receptors: a complexity of GABA_B-mediated signaling

γ-aminobutyric acid type B (GABA_B) receptors are broadly expressed in the nervous system and play an important role in neuronal excitability. GABA_B receptors are G protein-coupled receptors that mediate slow and prolonged inhibitory action, via activation of Gαi/o-type proteins. GABA_B receptors mediate their inhibitory action through activating inwardly rectifying K⁺ channels, inactivating voltage-gated Ca²⁺ channels, and inhibiting adenylate cyclase. Functional GABA_B receptors are obligate heterodimers formed by the co-assembly of R1 and R2 subunits. It is well established that GABA_B receptors interact not only with G proteins and effectors but also with various proteins. This review summarizes the structure, subunit isoforms, and function of GABA_B receptors, and discusses the complexity of GABA_B receptors, including how receptors are localized in specific subcellular compartments, the mechanism regulating cell surface expression and mobility of the receptors, and the diversity of receptor signaling through receptor crosstalk and interacting proteins.