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Spontaneous Na+ Transients in Individual Mitochondria of Intact Astrocytes

G. Azarias, D. Van De Ville, M. Unser, J.-Y. Chatton

Glia, vol. 56, no. 3, pp. 342-353, February 2008.

Mitochondria in intact cells maintain low Na+ levels despite the large electrochemical gradient favoring cation influx into the matrix. In addition, they display individual spontaneous transient depolarizations. We report here that individual mitochondria in living astrocytes exhibit spontaneous increases in their Na+ concentration (Namit+ spiking), as measured using the mitochondrial probe CoroNa Red. In a field of view with ∼30 astrocytes, up to 1,400 transients per minute were typically detected under resting conditions. Namit+ spiking was also observed in neurons, but was scarce in two nonneural cell types tested. Astrocytic Namit+ spikes averaged 12.2 ± 0.8 s in duration and 35.5 ± 3.2 mM in amplitude and coincided with brief mitochondrial depolarizations; they were impaired by mitochondrial depolarization and ruthenium red pointing to the involvement of a cation uniporter. Namit+ spiking activity was significantly inhibited by mitochondrial Na+/H+ exchanger inhibition and sensitive to cellular pH and Na+ concentration. Ca2+ played a permissive role on Namit+ spiking activity. Finally, we present evidence suggesting that Namit+ spiking frequency was correlated with cellular ATP levels. This study shows that, under physiological conditions, individual mitochondria in living astrocytes exhibit fast Na+ exchange across their inner membrane, which reveals a new form of highly dynamic and localized functional regulation.

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AUTHOR="Azarias, G. and Van De Ville, D. and Unser, M. and Chatton,
TITLE="Spontaneous ${\mathrm{Na}}^{+}$ Transients in Individual
        Mitochondria of Intact Astrocytes",

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