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

Boitier, Eric, Rea, Ruth and Duchen, Michael R (1999) Mitochondria exert a negative feedback on the propagation of intracellular Ca2+ waves in rat cortical astrocytes. Journal of Cell Biology, 145 (4). pp. 795-808. ISSN 0021-9525

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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 (Δψm, 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 Δψm 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.

Item Type: Article
Additional Information: Department of Physiology, UCL, London, UK
Schools and Departments: School of Life Sciences > Neuroscience
Subjects: Q Science > QP Physiology > QP0351 Neurophysiology and neuropsychology
Depositing User: Ruth Staras
Date Deposited: 14 Jun 2013 14:17
Last Modified: 21 Jun 2013 08:32
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