Format

Send to

Choose Destination
J Biol Chem. 2010 Oct 8;285(41):31107-19. doi: 10.1074/jbc.M109.082073. Epub 2010 Jul 28.

Temporary sequestration of potassium by mitochondria in astrocytes.

Author information

1
Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.

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, 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.

PMID:
20667836
PMCID:
PMC2951184
DOI:
10.1074/jbc.M109.082073
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center