Contribution of chloride channels to volume regulation of cortical astrocytes.
Parkerson, Kimberly A., and Harald Sontheimer.
Department of Neurobiology, Civitan International Research Center, University of
Alabama at Birmingham, Birmingham, Alabama 35294
APStracts 10:0068C, 2003.
The objective of this study was to determine the relative contribution of Cl«minus»
channels to volume regulation of cultured rat cortical astrocytes after hypotonic cell
swelling. Using a Coulter counter, we showed that cortical astrocytes regulate their cell
volume by ~60% within 45 min after hypotonic challenge. This volume regulation was
supported when Cl«minus» was replaced with Br«minus», «no3»,
methanesulfonate«minus», or acetate«minus» but was inhibited when Cl«minus» was
replaced with isethionate«minus» or gluconate«minus». Additionally, substitution of
Cl«minus» with I«minus» completely blocked volume regulation. Volume regulation was
unaffected by furosemide or bumetanide, blockers of KCl transport, but was inhibited by
Cl«minus» channel blockers, including 5-nitro-2-(3-phenylpropylamino)benzoic acid
(NPPB), «dids» (DIDS), and niflumic acid. Surprisingly, the combination of Cd2+ with
NPPB, DIDS, or niflumic acid inhibited regulation to a greater extent than any of these
drugs alone. Volume regulation did not differ among astrocytes cultured from different
brain regions, as cerebellar and hippocampal astrocytes exhibited behavior identical to
that of cortical astrocytes. These data suggest that Cl«minus» flux through ion channels
rather than transporters is essential for volume regulation of cultured astrocytes in
response to hypotonic challenge.
Received 26 December 2002; accepted in final form 17 February 2003
APS Manuscript Number C603-2.
Article publication pending Am J Physiol Cell Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 25 March 2003