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 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 inactivation kinetics at depolarized voltage potentials than TTX-S sodium currents (0.76 vs. 1.128 ms, at -10 mV; P < 0.0004).
Macfarlane
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Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0021, USA.
Sontheimer
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D001253:Astrocytes / Q000187:drug effects*; D055592:Biophysical Phenomena; D001703:Biophysics; D002478:Cells, Cultured; D002921:Cicatrix / Q000473:pathology; D005911:Gliosis / Q000209:etiology / Q000473:pathology*; D007700:Kinetics; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D013314:Stress, Mechanical; D013779:Tetrodotoxin / Q000494:pharmacology*
D015222:Sodium Channels; D013779:Tetrodotoxin