Rapid Ca2+-dependent increase in oxygen consumption by mitochondria in single mammalian central neurons

Oxygen consumption increases within a fraction of a second after the onset of neuronal activity, a phenomenon referred to as the “initial dip” in functional imaging studies of the living brain. The cellular mechanism that underlies this rapid increase in oxygen consumption has remained unclear, however. We have now used two-photon excitation imaging to characterize rapid activity-dependent mitochondrial responses in single neurons. This approach allowed simultaneous multicolor imaging of individual mitochondria in single mouse Purkinje neurons in culture. Mitochondrial depolarization was induced immediately when the cytosolic free Ca2+ concentration ([Ca2+]i) exceeded 15 μM and was associated with oxidation of mitochondrial NAD(P)H, suggesting that Ca2+-induced mitochondrial depolarization mediated by the Ca2+ uniporter directly facilitated oxidation of NAD(P)H. With the use of a miniature oxygen electrode, we detected a burst of oxygen consumption within 0.2 s after the onset of cell depolarization in single Purkinje neurons, and this rapid increase in oxygen consumption was dependent on the increase in [Ca2+]i. We have thus demonstrated a rapid Ca2+-dependent consumption of oxygen that is mediated by mitochondrial depolarization in mammalian central neurons. This process might function as a rapid feed-forward mechanism in homeostatic control of the cytosolic ATP concentration.