期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 285, 期 41, 页码 31107-31119出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.082073
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资金
- Heart and Stroke Foundation of British Columbia and Yukon
- Canadian Institutes of Health Research [MOP-77616]
- Canadian Institutes of Health Research-Vancouver Coastal Health Research Institute
- Michael Smith Foundation for Health Research
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-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.
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