ELECTROPHYSIOLOGICAL CHANGES THAT ACCOMPANY REACTIVE GLIOSIS IN-VITRO

An in vitro injury model was used to examine the electrophysiological changes that accompany reactive gliosis. Mechanical scarring of conflu ent spinal cord astrocytes led to a threefold increase in the prolifer ation of scar-associated astrocytes, as judged by bromodeoxyuridine (B rdU) labeling. Whole-cell patch-clamp recordings demonstrated that cur rent profiles differed absolutely between nonproliferating (BrdU(-)) a nd proliferating (BrdU(+)) astrocytes. The predominant current type ex pressed in BrdU(-) cells was an inwardly rectifying K+ current (K-IR; 1.3 pS/pF). BrdU(-) cells also expressed transient outward K+ currents , accounting for less than one-third of total K+ conductance (G). In c ontrast, proliferating BrdU(+) astrocytes exhibited a dramatic, approx imately threefold reduction in K-IR (0.45 pS/pF) but showed a twofold increase in the conductance of both transient (K-A) (0.67-1.32 pS/pF) and sustained (K-D) (0.42-1.10 pS/pF) outwardly rectifying K+ currents , with a G(KIR):G(KD) ratio of 0.4. Relative expression of G(KIR):G(KD ) 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), t he 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 K-IR, returning to control conductances within 24 hr. These differenc es between proliferating and nonproliferating astrocytes are reminisce nt of electrophysiological changes observed during gliogenesis, sugges ting that astrocytes undergoing secondary, injury-induced proliferatio n recapitulate the properties of immature glial cells. The switch in p redominance from K-IR to K-D appears to be essential for proliferation and scar repair, because both processes were inhibited by blockade of K-D.