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GABAB Receptor Coupling to G-proteins and Ion Channels

2010; Elsevier BV; Linguagem: Inglês

10.1016/s1054-3589(10)58006-2

1557-8925

Claire L. Padgett, Paul A. Slesinger,

Nicotinic Acetylcholine Receptors Study

GABAB receptors have been found to play a key role in regulating membrane excitability and synaptic transmission in the brain. The GABAB receptor is a G-protein coupled receptor (GPCR) that associates with a subset of G-proteins (pertussis toxin sensitive Gi/o family), that in turn regulate specific ion channels and trigger cAMP cascades. In this review, we describe the relationships between the GABAB receptor, its effectors and associated proteins that mediate GABAB receptor function within the brain. We discuss a unique feature of the GABAB receptor, the requirement for heterodimerization to produce functional receptors, as well as an increasing body of evidence that suggests GABAB receptors comprise a macromolecular signaling heterocomplex, critical for efficient targeting and function of the receptors. Within this complex, GABAB receptors associate specifically with Gi/o G-proteins that regulate voltage-gated Ca2+ (CaV) channels, G-protein activated inwardly rectifying K+ (GIRK) channels, and adenylyl cyclase. Numerous studies have revealed that lipid rafts, scaffold proteins, targeting motifs in the receptor, and regulators of G-protein signaling (RGS) proteins also contribute to the function of GABAB receptors and affect cellular processes such as receptor trafficking and activity-dependent desensitization. This complex regulation of GABAB receptors in the brain may provide opportunities for new ways to regulate GABA-dependent inhibition in normal and diseased states of the nervous system.