Spinal cord astrocytes display a switch from TTX-sensitive to TTX-resistant sodium currents after injury-induced gliosis in vitro

Journal of Neurophysiology
S N MacFarlane, H Sontheimer

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. 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 tetrodotoxin-sensitive(TTX-S, IC50 8 nM) to being approximately 40-fold more TTX-resistant (TTX-R,IC50 314 nM). These changes occurred within 6 h 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 </= 0. 003), and TTX-R currents have more depolarized V1/2 of activation (-33 vs. -23 mV). The V1/2 of inactivation was slightly, but not significantly, more depolarized for TTX-R currents as compared to TTX-S (-63 vs. -68 mV). Most notably, TTX-R currents showed significantly slower in...Continue Reading

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Citations

Feb 12, 2010·Brain : a Journal of Neurology·Joel A BlackStephen G Waxman
Oct 13, 2006·Pflügers Archiv : European journal of physiology·Helena NeprasovaEva Sykova
Feb 27, 2016·Glia·Laura W PappalardoStephen G Waxman
Apr 13, 2000·Brain Research. Brain Research Reviews·A Verkhratsky, C Steinhäuser
Oct 22, 2013·Neuron·Joel A Black, Stephen G Waxman

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