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J Neurophysiol 79: 2222-2226, 1998;
0022-3077/98 $5.00
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The Journal of Neurophysiology Vol. 79 No. 4 April 1998, pp. 2222-2226
Copyright ©1998 The American Physiological Society

RAPID COMMUNICATION


Spinal Cord Astrocytes Display a Switch From TTX-Sensitive to TTX-Resistant Sodium Currents After Injury-Induced Gliosis In Vitro

Stacey Nee Macfarlane and Harald Sontheimer

Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0021

MacFarlane, Stacey Nee and Harald Sontheimer. Spinal cord astrocytes display a switch from TTX-sensitive to TTX-resistant sodium currents after injury-induced gliosis in vitro. J. Neurophysiol. 79: 2222-2226, 1998. 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 ~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 inactivation kinetics at depolarized voltage potentials than TTX-S sodium currents (0.76 vs. 1.128 ms, at -10 mV; P < 0.0004).




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L. J. Rosenberg, Y. D. Teng, and J. R. Wrathall
Effects of the Sodium Channel Blocker Tetrodotoxin on Acute White Matter Pathology After Experimental Contusive Spinal Cord Injury
J. Neurosci., July 15, 1999; 19(14): 6122 - 6133.
[Abstract] [Full Text] [PDF]




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