Title | Metabolic communication between astrocytes and neurons via bicarbonate-responsive soluble adenylyl cyclase. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Choi HB, Gordon GRJ, Zhou N, Tai C, Rungta RL, Martinez J, Milner TA, Ryu JK, McLarnon JG, Tresguerres M, Levin LR, Buck J, MacVicar BA |
Journal | Neuron |
Volume | 75 |
Issue | 6 |
Pagination | 1094-104 |
Date Published | 2012 Sep 20 |
ISSN | 1097-4199 |
Keywords | 1-Methyl-3-isobutylxanthine, 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid, Adenylyl Cyclases, Animals, Animals, Newborn, Astrocytes, Bicarbonates, Coumaric Acids, Cyclic AMP, Dose-Response Relationship, Drug, Excitatory Postsynaptic Potentials, Glial Fibrillary Acidic Protein, Glucose, Glycogen, Green Fluorescent Proteins, Hippocampus, In Vitro Techniques, Lactic Acid, Microscopy, Immunoelectron, Microtubule-Associated Proteins, Models, Biological, Monocarboxylic Acid Transporters, Neurons, Patch-Clamp Techniques, Phosphodiesterase Inhibitors, Potassium, Rats, Rats, Sprague-Dawley, Sodium Channel Blockers, Tetrodotoxin |
Abstract | Astrocytes are proposed to participate in brain energy metabolism by supplying substrates to neurons from their glycogen stores and from glycolysis. However, the molecules involved in metabolic sensing and the molecular pathways responsible for metabolic coupling between different cell types in the brain are not fully understood. Here we show that a recently cloned bicarbonate (HCO₃⁻) sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and becomes activated in response to HCO₃⁻ entry via the electrogenic NaHCO₃ cotransporter (NBC). Activated sAC increases intracellular cAMP levels, causing glycogen breakdown, enhanced glycolysis, and the release of lactate into the extracellular space, which is subsequently taken up by neurons for use as an energy substrate. This process is recruited over a broad physiological range of [K⁺](ext) and also during aglycemic episodes, helping to maintain synaptic function. These data reveal a molecular pathway in astrocytes that is responsible for brain metabolic coupling to neurons. |
DOI | 10.1016/j.neuron.2012.08.032 |
Alternate Journal | Neuron |
PubMed ID | 22998876 |
PubMed Central ID | PMC3630998 |
Grant List | R01 HD038722 / HD / NICHD NIH HHS / United States R01 GM062328 / GM / NIGMS NIH HHS / United States / / Canadian Institutes of Health Research / Canada R01 NS055255 / NS / NINDS NIH HHS / United States R01 HD059913 / HD / NICHD NIH HHS / United States |