We have located links that may give you full text access.
Journal Article
Research Support, Non-U.S. Gov't
Neuronal Chloride Regulation via KCC2 Is Modulated through a GABA B Receptor Protein Complex.
Journal of Neuroscience 2017 May 32
GABAB receptors are G-protein-coupled receptors that mediate inhibitory synaptic actions through a series of downstream target proteins. It is increasingly appreciated that the GABAB receptor forms part of larger signaling complexes, which enable the receptor to mediate multiple different effects within neurons. Here we report that GABAB receptors can physically associate with the potassium-chloride cotransporter protein, KCC2, which sets the driving force for the chloride-permeable ionotropic GABAA receptor in mature neurons. Using biochemical, molecular, and functional studies in rodent hippocampus, we show that activation of GABAB receptors results in a decrease in KCC2 function, which is associated with a reduction in the protein at the cell surface. These findings reveal a novel "crosstalk" between the GABA receptor systems, which can be recruited under conditions of high GABA release and which could be important for the regulation of inhibitory synaptic transmission. SIGNIFICANCE STATEMENT Synaptic inhibition in the brain is mediated by ionotropic GABAA receptors (GABAA Rs) and metabotropic GABAB receptors (GABAB Rs). To fully appreciate the function and regulation of these neurotransmitter receptors, we must understand their interactions with other proteins. We describe a novel association between the GABAB R and the potassium-chloride cotransporter protein, KCC2. This association is significant because KCC2 sets the intracellular chloride concentration found in mature neurons and thereby establishes the driving force for the chloride-permeable GABAA R. We demonstrate that GABAB R activation can regulate KCC2 at the cell surface in a manner that alters intracellular chloride and the reversal potential for the GABAA R. Our data therefore support an additional mechanism by which GABAB Rs are able to modulate fast synaptic inhibition.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app