Ca²⁺ signals of astrocytes are modulated by the NAD⁺/NADH redox state.

Astrocytes are important glial cells in the brain providing metabolic support to neurons as well as contributing to brain signaling. These different functional levels have to be highly coordinated to allow for proper cell and brain function. In this study, we show that in astrocytes the NAD+/NADH redox state modulates dopamine-induced Ca2+ signals thereby connecting metabolism and Ca2+ signaling. Application of dopamine induced a dose-dependent increase in Ca2+ signal frequency in these cells, which was dependent on D1-receptor signaling, glycolytic activity, an increase in cytosolic NADH and inositol 1,4,5-triphosphate receptor operated intracellular Ca2+ stores. Application of dopamine at a low concentration (1 mu M) did not induce an increase in Ca2+ signal frequency by itself. However, simultaneously increasing cytosolic NADH content either by direct application of NADH or by application of lactate resulted in a pronounced increase in Ca2+ signal frequency. This increase could be blocked by co-application of pyruvate, suggesting that indeed the NAD+/NADH redox state is regulating Ca2+ signals. We conclude that at the NAD+/NADH redox state metabolic and signaling information is integrated in astrocytes, thereby most likely contributing to precisely coordinate these different tasks of astrocytes.