title: Separate domains for desensitization of GABA rho 1 and beta 2 subunits expressed in Xenopus oocytes.
abstract: Desensitization of ligand-gated receptor channels is an intrinsic feedback mechanism and prevents the receptor/channels from becoming overly activated thereby maintaining biological function of the nervous system. Desensitization also plays an important role in neuronal plasticity. By taking advantage of biophysical and pharmacological diversities of GABA beta2 subunits from the brain and rho1 subunits from the retina, structural determinants that confer agonist-induced desensitization were identified. A synthetic chimeric receptor/channel was created from the beta2 and rho1 subunits for this investigation. The chimera was constructed from the extracellular N-domain of the beta2 subunit, extending from the amino terminus to the beginning region of the M1 transmembrane segment, and from the C-domain of the rho1 subunit extending from the M1 transmembrane segment to the carboxyl terminus. The C-domain region included the M1 to M4 transmembrane regions and the large intracellular loop between the M3 and M4 transmembrane segments. Homo-oligomeric GABA beta2, rho1, and beta2/rho1 chimeric receptor/channels were individually expressed in Xenopus oocytes, and the desensitization characteristics attributable to each type of subunit were compared. Results from the present study reveal that motifs in the amino-terminal and carboxyl-terminal domains of the beta2 subunit conferred the agonist-induced desensitization; chloroform modulation was linked to specific phases of the GABA-activated current decay.
authors.affiliation: Department of Physiology and Biophysics, Wright State University, School of Medicine, Dayton, OH 45435, USA.
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002725:Chloroform / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D058785:GABA-A Receptor Agonists; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism*; D010424:Pentobarbital / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D018075:RNA, Complementary / Q000494:pharmacology; D051381:Rats; D018079:Receptors, GABA / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000235:genetics; D018080:Receptors, GABA-B; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000235:genetics; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D058785:GABA-A Receptor Agonists; C106350:GABRR2 protein, human; C491397:Gabrr2 protein, rat; D018075:RNA, Complementary; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D011993:Recombinant Fusion Proteins; D005680:gamma-Aminobutyric Acid; D002725:Chloroform; D010424:Pentobarbital