Temporary Sequestration of Potassium by Mitochondria in Astrocytes |
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Authors: | Michael G Kozoriz John Church Mark A Ozog Christian C Naus Claudia Krebs |
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Institution: | From the Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada |
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Abstract: | Increases in extracellular potassium concentration (K+]o), which can occur during neuronal activity and under pathological conditions such as ischemia, lead to a variety of potentially detrimental effects on neuronal function. Although astrocytes are known to contribute to the clearance of excess K+o, the mechanisms are not fully understood. We examined the potential role of mitochondria in sequestering K+ in astrocytes. Astrocytes were loaded with the fluorescent K+ indicator PBFI and release of K+ from mitochondria into the cytoplasm was examined after uncoupling the mitochondrial membrane potential with carbonyl cyanide m-chlorophenylhydrazone (CCCP). Under the experimental conditions employed, transient applications of elevated K+]o led to increases in K+ within mitochondria, as assessed by increases in the magnitudes of cytoplasmic K+] (K+]i) transients evoked by brief exposures to CCCP. When mitochondrial K+ sequestration was impaired by prolonged application of CCCP, there was a robust increase in K+]i upon exposure to elevated K+]o. Blockade of plasmalemmal K+ uptake routes by ouabain, Ba2+, or a mixture of voltage-activated K+ channel inhibitors reduced K+ uptake into mitochondria. Also, reductions in mitochondrial K+ uptake occurred in the presence of mito-KATP channel inhibitors. Rises in K+]i evoked by brief applications of CCCP following exposure to high K+]o were also reduced by gap junction blockers and in astrocytes isolated from connexin43-null mice, suggesting that connexins also play a role in K+ uptake into astrocyte mitochondria. We conclude that mitochondria play a key role in K+o handling by astrocytes. |
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Keywords: | Channel/Other Cell Junctions Connexin Mitochondria Neurobiology Astrocyte Buffering Gap Junction Potassium |
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