Temporary Sequestration of Potassium by Mitochondria in Astrocytes
| Autor: | Mark A. Ozog, John Church, Claudia Krebs, Christian C. Naus, Michael G. Kozoriz |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Carbonyl Cyanide m-Chlorophenyl Hydrazone
Mitochondrion Biology Carbonyl cyanide m-chlorophenyl hydrazone Biochemistry Cell junction Ouabain Mice chemistry.chemical_compound Neurobiology Ethers Cyclic medicine Animals Molecular Biology Cells Cultured Benzofurans Membrane Potential Mitochondrial Mice Knockout Membrane potential Uncoupling Agents Gap junction Cell Biology Potassium channel Mitochondria medicine.anatomical_structure chemistry Potassium Channels Voltage-Gated Astrocytes Connexin 43 Potassium Biophysics Astrocyte medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 285:31107-31119 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m109.082073 |
| Popis: | 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, Ba(2+), 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-K(ATP) 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. |
| Databáze: | OpenAIRE |
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