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Mitochondria Exert a Negative Feedback on the Propagation of Intracellular Ca2+ Waves in Rat Cortical Astrocytes

By May 2, 2018Mitochondria

Mitochondria Exert a Negative Feedback on the Propagation of
Intracellular Ca2+ Waves in Rat Cortical Astrocytes

Eric Boitier, Ruth Rea, and Michael R. Duchen

We have used digital fluorescence imaging techniques to explore the interplay between mitochondrial Ca2+ uptake and physiological Ca2+ signaling in rat cortical astrocytes. A rise in cytosolic Ca2+ ([Ca2+]cyt), resulting from mobilization of ER Ca2+ stores was followed by a rise in mitochondrial Ca2+ ([Ca2+]m, monitored using rhod-2). Whereas [Ca2+]cyt recovered within ~1 min, the time to recovery for [Ca2+]m was ~30 min. Dissipating the mitochondrial membrane potential ( Dcm, using the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxy-phenylhydrazone [FCCP] with oligomycin) prevented mitochondrial Ca2+ uptake and slowed the rate of decay of [Ca2+]cyt transients, suggesting that mitochondrial Ca2+ uptake plays a significant role in the clearance of physiological [Ca2+]cyt loads in astrocytes. Ca2+ signals in these cells initiated either by receptor-mediated ER Ca2+ release or mechanical stimulation often consisted of propagating waves (measured using fluo-3). In response to either stimulus, the wave traveled at a mean speed of 22.9 6 11.2 mm/s (n 5 262). This was followed by a wave of mitochondrial depolarization (measured using tetramethylrhodamine ethyl ester [TMRE]), consistent with Ca2+ uptake into mitochondria as the Ca2+ wave traveled across the cell. Collapse of Dcm to prevent mitochondrial Ca2+ uptake significantly increased the rate of propagation of the Ca2+ waves by 50%. Taken together, these data suggest that cytosolic Ca2+ buffering by mitochondria provides a potent mechanism to regulate the localized spread of astrocytic Ca2+ signals.

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