GABAB receptor attenuation of GABAA currents in neurons of the mammalian central nervous system

Wen Shen, Changlong Nan, Peter T. Nelson, Harris Ripps, Malcolm M. Slaughter

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 GABAB receptor can suppress the ionotropic GABAA receptor current, in both the in vitro mouse retina and in human amygdala membrane fractions. Expression of amygdala membrane microdomains in Xenopus oocytes by microtransplantation produced functional ionotropic and metabotropic GABA receptors. Most GABAA receptors had properties of α-subunit containing receptors, with ~5% having ρ-subunit properties. Only GABAA receptors with α-subunit-like properties were regulated by GABAB receptors. In mouse retinal ganglion cells, where only α-subunit-containing GABAA receptors are expressed, GABAB receptors suppressed GABAA receptor currents. This suppression was blocked by GABAB receptor antagonists, G-protein inhibitors, and GABAB receptor antibodies. Based on the kinetic differences between metabotropic and ionotropic receptors, their interaction would suppress repeated, rapid GABAergic inhibition.

Original languageEnglish
Article numbere13129
JournalPhysiological Reports
Volume5
Issue number6
DOIs
StatePublished - Mar 1 2017

Bibliographical note

Funding Information:
Funding Information This study was supported by grants from the National Science Foundation (NSF, IOS-1021646, to W. S.) and the National Eye Institute (NEI), NIH (EY 14161, to W. S.).

Publisher Copyright:
© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Keywords

  • GABA receptors
  • GABA receptors
  • human amygdala
  • mouse retina
  • ρ-subunit GABA receptors

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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