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NBCe1 mediates the regulation of the NADH/NAD + redox state in cortical astrocytes by neuronal signals
Author(s) -
Köhler Susanne,
Winkler Ulrike,
Sicker Marit,
Hirrlinger Johannes
Publication year - 2018
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23504
Subject(s) - nad+ kinase , biology , biochemistry , redox , glutamate receptor , intracellular , cytosol , astrocyte , neuroglia , glycerol 3 phosphate dehydrogenase , extracellular , oxidative phosphorylation , metabolism , microbiology and biotechnology , chemistry , enzyme , neuroscience , receptor , central nervous system , organic chemistry
Astrocytes are a glial cell type, which is indispensable for brain energy metabolism. Within cells, the NADH/NAD + redox state is a crucial node in metabolism connecting catabolic pathways to oxidative phosphorylation and ATP production in mitochondria. To characterize the dynamics of the intracellular NADH/NAD + redox state in cortical astrocytes Peredox, a genetically encoded sensor for the NADH/NAD + redox state, was expressed in cultured cortical astrocytes as well as in cortical astrocytes in acutely isolated brain slices. Calibration of the sensor in cultured astrocytes revealed a mean basal cytosolic NADH/NAD + redox ratio of about 0.01; however, with a broad distribution and heterogeneity in the cell population, which was mirrored by a heterogeneous basal cellular concentration of lactate. Inhibition of glucose uptake decreased the NADH/NAD + redox state while inhibition of lactate dehydrogenase or of lactate release resulted in an increase in the NADH/NAD + redox ratio. Furthermore, the NADH/NAD + redox state was regulated by the extracellular concentration of K + , and application of the neurotransmitters ATP or glutamate increased the NADH/NAD + redox state dependent on purinergic receptors and glutamate uptake, respectively. This regulation by K + , ATP, and glutamate involved NBCe1 mediated sodium‐bicarbonate transport. These results demonstrate that the NADH/NAD + redox state in astrocytes is a metabolic node regulated by neuronal signals reflecting physiological activity, most likely contributing to adjust astrocytic metabolism to energy demand of the brain.