Premium
Regulation of Kv1.3 expression by C5b‐9 terminal complex in oligodendrocytes and their role cell cycle activation
Author(s) -
Cudrici Cornelia Diana,
Soloviova Kateryna,
Rozycka Monika,
Tegla Cosmin Adrian,
Judge Susan,
Rus Horea
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.673.2
Subject(s) - pertussis toxin , cell cycle , microbiology and biotechnology , biology , cell growth , protein kinase b , phosphorylation , chemistry , signal transduction , cell , biochemistry , g protein
Proliferative oligodendrocytes progenitors cells (OPC) express various potassium (K + ) channels including K v 1.3 required for the G1/S transition. In contrast, mature oligodendrocytes (OLG) exhibit few K v 1.3 channels. We examined K v 1.3 expression in OLG and the effect of C5b‐9 on K v 1.3 expression. K v 1.3 was found to be expressed in rat OPC, with differentiated OLG exhibiting little K v 1.3. Exposure to purified C5b‐9 significantly increased K v 1.3 expression while C5b6 had no effect. To test functionality, we blocked K v 1.3 in C5b‐9 stimulated OLG using the recombinant scorpion toxin rOsK‐1 ( Orthochirus scrobiculosus ) and found that this K + channel blocker abolished K v 1.3 expression. K v 1.3 expression was also inhibited by Pertussis toxin indicating the requirement of Gi‐protein. Interestingly, Akt phosphorylation and activation by C5b‐9 was also inhibited by rOsK‐1 strongly suggesting a role for K v 1.3 in controlling C5b‐9 downstream signaling pathways. Since Akt play a major role in C5b‐9 induced cell cycle activation we investigated the effect of inhibiting K v 1.3 on DNA synthesis. Pretreatment with rOsK‐1 significantly inhibited 3 [H]‐Thymidine incorporation induced by C5b‐9 in OLG, indicating that K v 1.3 plays an important role in C5b‐9 induced DNA synthesis. In conclusion, our data suggest that K v 1.3 plays an important role in C5b‐9 OLG cell cycle activation and survival in an inflammatory milieu.