Mitochondrial polarization in rat hippocampal astrocytes is resistant to cytosolic Ca 2+ loads

Abstract The influence of physiological Ca 2+ ‐inducing stimuli and agents mimicking ischemic conditions on mitochondrial potential was studied in postnatal (P1) hippocampal astrocytes. Cytosolic Ca 2+ loads with characteristic kinetics of rise and duration, detected by Fura‐2, were provoked by extr...

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Published in:Journal of neuroscience research 2001-12, Vol.66 (5), p.1019-1027
Main Authors: Kahlert, Stefan, Schild, Lorenz, Reiser, Georg
Format: Article
Language:English
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Summary:Abstract The influence of physiological Ca 2+ ‐inducing stimuli and agents mimicking ischemic conditions on mitochondrial potential was studied in postnatal (P1) hippocampal astrocytes. Cytosolic Ca 2+ loads with characteristic kinetics of rise and duration, detected by Fura‐2, were provoked by extracellular Ca 2+ influx, release from InsP 3 ‐sensitive intracellular stores, or inhibition of the reloading of endoplasmic reticulum Ca 2+ stores. Inhibitors of mitochondrial respiration caused only moderate release of Ca 2+ from intracellular stores, inducing a rise of less than 60 nM. The maximal Ca 2+ rise was found with InsP 3 ‐mediated responses (500 nM; via ATP) or with ionophore (4‐Br‐A23187)‐mediated Ca 2+ influx from extracellular medium (770 nM). Remarkably, all these agents causing significant rise of cytosolic Ca 2+ , only minimally depolarized the mitochondria. Membrane potential of mitochondria was monitored by Rh123 or TMRE. Depolarization was only found with very high cytosolic Ca 2+ levels (above 60 μM; measured by fura FF). These were achieved with external Ca 2+ influx by ionophore in combination with inhibition of glycolysis. Thus, mitochondria in the astrocytes are obviously not sensitive to moderate cytosolic Ca 2+ loads, irrespective of the source of Ca 2+ . Furthermore, isolated rat brain mitochondria display a low sensitivity of respiratory activity to Ca 2+ , which is consistent with the data obtained with the astrocytes in vitro. The capacity of isolated mitochondria to build up a potential was gradually reduced at low micromolar Ca 2+ and totally compromised only at Ca 2+ concentrations in the 100 μM range. © 2001 Wiley‐Liss, Inc.
ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.10052