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Mitochondria exert a negative feedback on the propagation of intracellular Ca2+ waves in rat cortical astrocytes

journal contribution
posted on 2023-06-08, 15:14 authored by Eric Boitier, Ruth Rea, 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 (??m, using the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxy-phenyl-hydrazone [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 ± 11.2 µm/s (n = 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 ??m 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.

History

Publication status

  • Published

Journal

Journal of Cell Biology

ISSN

0021-9525

Publisher

Rockefeller University Press

Issue

4

Volume

145

Page range

795-808

Department affiliated with

  • Neuroscience Publications

Notes

Department of Physiology, UCL, London, UK

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2013-06-14

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