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Physiol Rep. 2017 Mar;5(6). pii: e13129. doi: 10.14814/phy2.13129.

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

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Department of Biomedical Science, Charles E. Schmidt College of Medicine Florida Atlantic University, Boca Raton, Florida
Department of Biomedical Science, Charles E. Schmidt College of Medicine Florida Atlantic University, Boca Raton, Florida.
Division of Neuropathology, Department of Pathology, University of Kentucky, Lexington, Kentucky.
Sanders-Brown Centre on Aging, University of Kentucky, Lexington, Kentucky.
Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine, Chicago, Illinois.
Whitman Investigator, Marine Biological Laboratory, Woods Hole, Massachusetts.
Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York.


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.


GABAA receptors; GABAB receptors; human amygdala; mouse retina; ρ‐subunit GABAA receptors

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