Journal
NEURON
Volume 75, Issue 6, Pages 1094-1104Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2012.08.032
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Funding
- Canadian Institutes of Health Research
- Transatlantic Networks of Excellence Program from the Foundation Leducq
- Arthur and June Wilms fellowship
- Heart and Stroke Foundation of Canada
- Alberta Heritage Foundation for Medical Research
- MSFHR
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- National Institutes of Health
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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.
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