title: GABABreceptor attenuation of GABAAcurrents in neurons of the mammalian central nervous system.
abstract: Ionotropic receptors are tightly regulated by second messenger systems and are often present along with their metabotropic counterparts on a neuron's plasma membrane. This leads to the hypothesis that the two receptor subtypes can interact, and indeed this has been observed in excitatory glutamate and inhibitory GABA receptors. In both systems the metabotropic pathway augments the ionotropic receptor response. However, we have found that the metabotropic GABABreceptor can suppress the ionotropic GABAAreceptor current, in both the in vitro mouse retina and in human amygdala membrane fractions. Expression of amygdala membrane microdomains inXenopusoocytes by microtransplantation produced functional ionotropic and metabotropic GABA receptors. Most GABAAreceptors had properties ofα-subunit containing receptors, with ~5% havingρ-subunit properties. Only GABAAreceptors withα-subunit-like properties were regulated by GABABreceptors. In mouse retinal ganglion cells, where onlyα-subunit-containing GABAAreceptors are expressed, GABABreceptors suppressed GABAAreceptor currents. This suppression was blocked by GABABreceptor antagonists, G-protein inhibitors, and GABABreceptor antibodies. Based on the kinetic differences between metabotropic and ionotropic receptors, their interaction would suppress repeated, rapid GABAergic inhibition.
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Medicine Florida Atlantic University, Boca Raton, Florida wshen@fau.edu.
authors.forename: Wen
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Medicine Florida Atlantic University, Boca Raton, Florida.
authors.forename: Changlong
authors.initials: C
authors.lastname: Nan
authors.affiliation: Division of Neuropathology, Department of Pathology, University of Kentucky, Lexington, Kentucky.|Sanders-Brown Centre on Aging, University of Kentucky, Lexington, Kentucky.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine, Chicago, Illinois.|Whitman Investigator, Marine Biological Laboratory, Woods Hole, Massachusetts.
authors.forename: Harris
authors.initials: H
authors.lastname: Ripps
authors.affiliation: Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Malcolm M
authors.initials: MM
authors.lastname: Slaughter
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D014981:Xenopus
chemical_list: D011963:Receptors, GABA-A; D018080:Receptors, GABA-B
keywords: GABAA receptors; GABAB receptors; human amygdala; mouse retina; ρ‐subunit GABAA receptors