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Intrinsic optical signals in the rat optic nerve: Role for K + uptake via NKCC1 and swelling of astrocytes
Author(s) -
Macvicar Brian A.,
Feighan Denise,
Brown Angus,
Ransom Bruce
Publication year - 2002
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10023
Subject(s) - extracellular , cotransporter , biophysics , stimulation , astrocyte , bumetanide , tetrodotoxin , optic nerve , biology , neuroglia , neuroscience , anatomy , microbiology and biotechnology , chemistry , central nervous system , sodium , organic chemistry
Measurements of extracellular space volume and imaging of intrinsic optical signals (IOSs) have shown that neuronal activity increases light transmittance by causing cellular swelling. However, the cellular mechanisms underlying these volume changes and the contribution of astrocyte swelling to the changes in tissue volume are unclear. In this study, we have investigated IOSs in optic nerves to analyze the mechanisms contributing to these signals in a system consisting of only axons and glial cells. We examined both intact optic nerves and enucleated optic nerves, which contained no axons and consisted primarily of astrocytes. Electrical stimulation of intact optic nerves evoked an increase in light transmittance, which was graded with increasing stimulation frequency and was mimicked by raising extracellular K + concentration ([K + ] o ). The stimulation‐induced IOS grew in amplitude and had a time course similar to extracellular space shrinkage. Tetrodotoxin (TTX) blocked the electrically induced but not the high K + ‐induced IOS. In enucleated nerves, light transmittance progressively increased in higher [K + ] o . The high [K + ] o ‐induced IOSs were reversibly depressed by furosemide and bumetanide, antagonists for Na‐K‐2Cl cotransport, but were unaltered by TTX. We also used a monoclonal antibody to the NKCC1 form of the Na‐K‐2Cl cotransporter to show that NKCC1 is expressed in optic nerves as shown in Western blotting and is colocalized in GFAP immunopositive astrocytes. In summary, these results indicated that KCl uptake into astrocytes via an Na‐K‐2Cl cotransporter during raised [K + ] o contributes to the generation of cellular swelling and the intrinsic optical signals. GLIA 37:114–123, 2002. © 2002 Wiley‐Liss, Inc.