title: Mechanisms of fast desensitization of GABA(B) receptor-gated currents.
abstract: GABA(B) receptors (GABA(B)Rs) regulate the excitability of most neurons in the central nervous system by modulating the activity of enzymes and ion channels. In the sustained presence of the neurotransmitter γ-aminobutyric acid, GABA(B)Rs exhibit a time-dependent decrease in the receptor response-a phenomenon referred to as homologous desensitization. Desensitization prevents excessive receptor influences on neuronal activity. Much work focused on the mechanisms of GABA(B)R desensitization that operate at the receptor and control receptor expression at the plasma membrane. Over the past few years, it became apparent that GABA(B)Rs additionally evolved mechanisms for faster desensitization. These mechanisms operate at the G protein rather than at the receptor and inhibit G protein signaling within seconds of agonist exposure. The mechanisms for fast desensitization are ideally suited to regulate receptor-activated ion channel responses, which influence neuronal activity on a faster timescale than effector enzymes. Here, we provide an update on the mechanisms for fast desensitization of GABA(B)R responses and discuss physiological and pathophysiological implications.
authors: Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland.
authors: Adi
authors: A
authors: Raveh
authors: Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland; Department of Auditory Neuroscience, Institute of Experimental Medicine, ASCR, Prague, Czech Republic.
authors: Rostislav
authors: R
authors: Turecek
authors: Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland. Electronic address: bernhard.bettler@unibas.ch.
authors: Bernhard
authors: B
authors: Bettler
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D019204:GTP-Binding Proteins
keywords: Acute desensitization; G protein-coupled receptor; G protein-coupled receptor kinase; GABA(B); KCTD12; RGS; Short-term desensitization