title: Electrophysiological changes that accompany reactive gliosis in vitro.
abstract: An in vitro injury model was used to examine the electrophysiological changes that accompany reactive gliosis. Mechanical scarring of confluent spinal cord astrocytes led to a threefold increase in the proliferation of scar-associated astrocytes, as judged by bromodeoxyuridine (BrdU) labeling. Whole-cell patch-clamp recordings demonstrated that current profiles differed absolutely between nonproliferating (BrdU-) and proliferating (BrdU+) astrocytes. The predominant current type expressed in BrdU- cells was an inwardly rectifying K+ current (KIR; 1.3 pS/pF). BrdU- cells also expressed transient outward K+ currents, accounting for less than one-third of total K+ conductance (G). In contrast, proliferating BrdU+ astrocytes exhibited a dramatic, approximately threefold reduction in KIR (0.45 pS/pF) but showed a twofold increase in the conductance of both transient (KA) (0.67-1. 32 pS/pF) and sustained (KD) (0.42-1.10 pS/pF) outwardly rectifying K+ currents, with a GKIR:GKD ratio of 0.4. Relative expression of GKIR:GKD led to more negative resting potentials in nonproliferating (-60 mV) versus proliferating astrocytes (-53 mV; p = 0.015). Although 45% of the nonproliferating astrocytes expressed Na+ currents (0.47 pS/pF), the majority of proliferating cells expressed prominent Na+ currents (0.94 pS/pF). Injury-induced electrophysiological changes are rapid and transient, appearing within 4 hr postinjury and, with the exception of KIR, returning to control conductances within 24 hr. These differences between proliferating and nonproliferating astrocytes are reminiscent of electrophysiological changes observed during gliogenesis, suggesting that astrocytes undergoing secondary, injury-induced proliferation recapitulate the properties of immature glial cells. The switch in predominance from KIR to KD appears to be essential for proliferation and scar repair, because both processes were inhibited by blockade of KD.
authors.affiliation: Department of Neurobiology, University of Alabama, Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: MacFarlane
authors.forename: H
authors.initials: H
authors.lastname: Sontheimer
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002921:Cicatrix / Q000473:pathology / Q000503:physiopathology; D004553:Electric Conductivity; D004594:Electrophysiology; D005911:Gliosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007473:Ion Channels / Q000378:metabolism; D011188:Potassium / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D007473:Ion Channels; D015221:Potassium Channels; D012964:Sodium; D001973:Bromodeoxyuridine; D011188:Potassium