Effect of elevated K(+), hypotonic stress, and cortical spreading depression on astrocyte swelling in GFAP-deficient mice
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
11494410
DOI
10.1002/glia.1084
PII: 10.1002/glia.1084
Knihovny.cz E-resources
- MeSH
- Astrocytes drug effects metabolism pathology MeSH
- Cell Membrane drug effects metabolism MeSH
- Diffusion drug effects MeSH
- Potassium metabolism pharmacology MeSH
- Extracellular Space drug effects metabolism MeSH
- Fluorescent Dyes pharmacokinetics MeSH
- Glial Fibrillary Acidic Protein deficiency genetics MeSH
- Intermediate Filaments drug effects metabolism pathology MeSH
- Isoquinolines pharmacokinetics MeSH
- Membrane Potentials drug effects physiology MeSH
- Patch-Clamp Techniques MeSH
- Spinal Cord drug effects metabolism pathology MeSH
- Mice, Knockout anatomy & histology metabolism MeSH
- Mice MeSH
- Osmotic Pressure drug effects MeSH
- Cell Membrane Permeability drug effects physiology MeSH
- Cortical Spreading Depression drug effects physiology MeSH
- Somatosensory Cortex metabolism physiopathology MeSH
- Cell Size drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Potassium MeSH
- Fluorescent Dyes MeSH
- Glial Fibrillary Acidic Protein MeSH
- Isoquinolines MeSH
- lucifer yellow MeSH Browser
Glial fibrillary acidic protein (GFAP) is the main component of intermediate filaments in astrocytes. To assess its function in astrocyte swelling, we compared astrocyte membrane properties and swelling in spinal cord slices of 8- to 10-day-old wild-type control (GFAP(+/+)) and GFAP-knockout (GFAP(-/-)) mice. Membrane currents and K(+) accumulation around astrocytes after a depolarizing pulse were studied using the whole-cell patch-clamp technique. In vivo cell swelling was studied in the cortex during spreading depression (SD) in 3 to 6-month-old animals. Swelling-induced changes of the extracellular space (ECS) diffusion parameters, i.e., volume fraction alpha and tortuosity lambda, were studied by the real-time iontophoretic tetramethylammonium (TMA(+)) method using TMA(+)-selective microelectrodes. Morphological analysis using confocal microscopy and quantification of xy intensity profiles in a confocal plane revealed a lower density of processes in GFAP(-/-) astrocytes than in GFAP(+/+) astrocytes. K(+) accumulation evoked by membrane depolarization was lower in the vicinity of GFAP(-/-) astrocytes than GFAP(+/+) astrocytes, suggesting the presence of a larger ECS around GFAP(-/-) astrocytes. Astrocyte swelling evoked by application of 50 mM K(+) or by hypotonic solution (HS) produced a larger increase in [K(+)](e) around GFAP(+/+) astrocytes than around GFAP(-/-) astrocytes. No differences in alpha and lambda in the spinal cord or cortex of GFAP(+/+) and GFAP(-/-) mice were found; however, the application of either 50 mM K(+) or HS in spinal cord, or SD in cortex, evoked a large decrease in alpha and an increase in lambda in GFAP(+/+) mice only. Slower swelling in GFAP(-/-) astrocytes indicates that GFAP and intermediate filaments play an important role in cell swelling during pathological states.
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Diffusion in brain extracellular space
