SPINAL-CORD ASTROCYTES DISPLAY A SWITCH FROM TTX-SENSITIVE TO TTX-RESISTANT SODIUM CURRENTS AFTER INJURY-INDUCED GLIOSIS IN-VITRO

Two distinct morphological subtypes of astrocytes have been shown to e xpress Na+ currents that differ biophysically and pharmacologically. U sing an in vitro model for reactive gliosis, we recently reported mark ed changes in Na+ and K+ channel expression by astrocytes induced to p roliferate. Using this in vitro assay in which a confluent monolayer o f astrocytes is mechanically scarred to induce gliosis, we now demonst rate that sodium currents of scar-associated cells, in addition to dou bling in current density, also switch from being tetrodotoxin-sensitiv e (TTX-S, IC50 8 nM) to being similar to 40-fold more TTX-resistant (T TX-R, IC50 314 nM). These changes occurred within 6 h after injury and were not associated with any notable changes in cell morphology. Chan ges in biophysical properties were analyzed for the two current types. The activation curve for TTX-R currents demonstrated a significant de polarized shift versus that of TTX-S currents (P less than or equal to 0.003), and TTX-R currents have more depolarized V-1/2 Of activation (-33 vs. -23 mV). The V-1/2 Of inactivation was slightly, but not sign ificantly, more depolarized for TTX-R currents as compared to TTX-S (- 63 vs. -68 mV). Most notably, TTX-R currents showed significantly slow er inactivation kinetics at depolarized voltage potentials than TTX-S sodium currents (0.76 vs. 1.128 ms, at -10 mV; P < 0.0004).