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

Boitier, E; Rea, R; Duchen, MR; (1999) Mitochondria exert a negative feedback on the propagation of intracellular Ca2+ waves in rat cortical astrocytes. J CELL BIOL , 145 (4) 795 - 808.

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Abstract

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 similar to 1 min, the time to recovery for [Ca2+](m) was similar to 30 min. Dissipating the mitochondrial membrane potential (Delta psi(m), 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 +/- 11.2 mu m/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 Delta psi(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.

Type: Article
Title: Mitochondria exert a negative feedback on the propagation of intracellular Ca2+ waves in rat cortical astrocytes
Keywords: intracellular Ca2+ waves, astrocytes, mitochondria, negative feedback, Ca2+ buffering, XENOPUS-LAEVIS OOCYTES, ROOT GANGLION NEURONS, CALCIUM WAVES, ENDOPLASMIC-RETICULUM, CULTURED ASTROCYTES, INOSITOL TRISPHOSPHATE, SPREADING DEPRESSION, ENDOTHELIAL-CELLS, ENERGY-METABOLISM, ADULT ASTROCYTES
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/154645
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