Spinal Cord Astrocytes Display a Switch from TTX-Sensitive to TTX-Resistant
Sodium Currents Following Injury Induced Gliosis In vitro.
Stacey Nee MacFarlane and Harald Sontheimer.
Department of Neurobiology, University of Alabama at Birmingham,
Birmingham, AL 35294-0021.
APStracts 4:373N, 1997.
ABSTRACT
Two distinct morphological subtypes of astrocytes have been shown to express
Na+ currents that differ biophysically and pharmacologically. Using an in
vitro model for reactive gliosis, we recently reported marked changes in Na+
and K+ channel expression by astrocytes induced to proliferate (MacFarlane and
Sontheimer 1997). Using this in vitro assay in which a confluent monolayer of
astrocytes is mechanically scarred to induce gliosis, we now demonstrate that
sodium currents of scar-associated cells, in addition to doubling in current
density, also switch from being TTX-Sensitive (TTX-S, IC50 8 nM) to being
about 40-fold more TTX-Resistant (TTX-R, IC50 314 nM). These changes occurred
within 6h after injury and were not associated with any notable changes in
cell morphology. Changes in biophysical properties were analyzed for the two
current types. The activation curve for TTX-R currents demonstrated a
significant depolarized shift versus that of TTX-S currents (p ó 0.003), and
TTX-R currents have more depolarized V1/2 of activation (-33 versus -23 mV).
The V1/2 of inactivation was slightly, but not significantly, more depolarized
for TTX-R currents as compared to TTX-S (-63 versus -68 mV). Most notably,
TTX-R currents showed significantly slower inactivation kinetics at
depolarized voltage potentials than TTX-S sodium currents (0.76 versus 1.128
ms, at -10 mV) (p < 0.0004).
Received 2 December 1997; accepted in final form 23 December 1997.
APS Manuscript Number J983-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 January 1998