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 Ca(2+) 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.