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.

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Published in Physiological Reports, v. 5, issue 6, e13129, p. 1-11.

© 2017 The Authors.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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This study was supported by grants from the National Science Foundation (NSF, IOS1021646, to W. S.) and the National Eye Institute (NEI), NIH (EY 14161, to W. S.).