Blog
About

6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Phospho-dependent functional modulation of GABA(B) receptors by the metabolic sensor AMP-dependent protein kinase.

      Neuron

      metabolism, immunology, chemistry, Receptors, GABA-B, Rats, Protein Isoforms, Potassium Channels, Inwardly Rectifying, Phosphorylation, Osmolar Concentration, Neurons, Immune Sera, Humans, Adenosine Monophosphate, Hippocampus, Cyclic AMP-Dependent Protein Kinases, Cells, Cultured, Cell Survival, pathology, Brain Ischemia, Brain, physiopathology, chemically induced, Anoxia, Animals

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          GABA(B) receptors are heterodimeric G protein-coupled receptors composed of R1 and R2 subunits that mediate slow synaptic inhibition in the brain by activating inwardly rectifying K(+) channels (GIRKs) and inhibiting Ca(2+) channels. We demonstrate here that GABA(B) receptors are intimately associated with 5'AMP-dependent protein kinase (AMPK). AMPK acts as a metabolic sensor that is potently activated by increases in 5'AMP concentration that are caused by enhanced metabolic activity, anoxia, or ischemia. AMPK binds the R1 subunit and directly phosphorylates S783 in the R2 subunit to enhance GABA(B) receptor activation of GIRKs. Phosphorylation of S783 is evident in many brain regions, and is increased dramatically after ischemic injury. Finally, we also reveal that S783 plays a critical role in enhancing neuronal survival after ischemia. Together our results provide evidence of a neuroprotective mechanism, which, under conditions of metabolic stress or after ischemia, increases GABA(B) receptor function to reduce excitotoxicity and thereby promotes neuronal survival.

          Related collections

          Author and article information

          Journal
          17224405
          2570046
          10.1016/j.neuron.2006.12.015

          Comments

          Comment on this article