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Independent mechanisms of potassium clearance by astrocytes in gliotic tissue
Author(s) -
Walz Wolfgang,
Wuttke Werner A.
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990615)56:6<595::aid-jnr5>3.0.co;2-5
Subject(s) - astrogliosis , extracellular , gliosis , neuroglia , glial fibrillary acidic protein , hippocampal formation , biophysics , astrocyte , chemistry , membrane potential , kainic acid , intracellular , lucifer yellow , neuroscience , gfap stain , dids , electrophysiology , microbiology and biotechnology , biology , biochemistry , central nervous system , gap junction , glutamate receptor , immunology , membrane , receptor , immunohistochemistry
The “glial impairment hypothesis” states that astrocytes which change from normal into the reactive type lose their ability to clear extracellular K + , which in turn leads to hyperexcitability in the gliotic tissue. As this hypothesis was never proven or disproven, the question of glial efficiency in K + clearance in gliotic tissue is still controversial, mainly due to the lack of direct measurements of the intracellular K + concentration of reactive astrocytes. In order to investigate K + accumulation by glial cells of gliotic tissue, we used hippocampal slices. Adult rats, previously treated with kainic acid, exhibited loss of neurons and gliosis in the CA1 layer of the hippocampus within 3 days. After this time period, double‐barrelled microelectrodes were used to inject Lucifer yellow into cells of the stratum radiatum of the CA1 subfield in 400‐μm‐thick hippocampal slices. These cells had electrophysiological and morphological characteristics of astrocytes. Most injected cells (70%) were dye‐coupled to other cells and were glial fibrillary acidic protein (GFAP)‐positive (80%). We found, however, that GFAP‐positive cells were dye‐coupled not only to each other, but also to GFAP‐negative cells. In another set of experiments, we investigated the glial membrane potential during reduction of the extracellular Cl − concentration and the use of the Cl − channel blocker 4,4′‐diisothiocyanostilbene‐2,2′ disulphonic acid (DIDS). The results suggest that reactive astrocytes have a significant resting Cl − conductance. K + ‐selective microelectrodes were used to analyze the intracellular glial K + concentration. When the extracellular K + concentration was increased from 3.5 mM to 10 mM, the intracellular K + concentration increased by 23 mM. Experiments in which different ion transport systems were blocked with ouabain and DIDS suggest that this increase is dependent on two mechanisms, which can substitute each other: the Na + , K + ‐ATPase and passive K + and anion fluxes. Inhibition of either of the two mechanisms did not block the K + uptake. If, however, the Na + , K + ‐ ATPase and Cl − channels were inhibited at the same time, the net accumulation of K + was blocked. It appears, therefore, that astrocytes in the gliotic stratum radiatum of the hippocampal slice have the capacity to limit increases in extracellular K + that are produced by hyperactive surviving hippocampal neurons by passive mechanisms and hence independently of blood and oxygen supply. J. Neurosci. Res. 56:595–603, 1999. © 1999 Wiley‐Liss, Inc.