title: C5b-9-activated, K(v)1.3 channels mediate oligodendrocyte cell cycle activation and dedifferentiation.
abstract: Voltage-gated potassium (K(v)) channels play an important role in the regulation of growth factor-induced cell proliferation. We have previously shown that cell cycle activation is induced in oligodendrocytes (OLGs) by complement C5b-9, but the role of K(v) channels in these cells had not been investigated. Differentiated OLGs were found to express K(v)1.4 channels, but little K(v)1.3. Exposure of OLGs to C5b-9 modulated K(v)1.3 functional channels and increased protein expression, whereas C5b6 had no effect. Pretreatment with the recombinant scorpion toxin rOsK-1, a highly selective K(v)1.3 inhibitor, blocked the expression of K(v)1.3 induced by C5b-9. rOsK-1 inhibited Akt phosphorylation and activation by C5b-9 but had no effect on ERK1 activation. These data strongly suggest a role for K(v)1.3 in controlling the Akt activation induced by C5b-9. Since Akt plays a major role in C5b-9-induced cell cycle activation, we also investigated the effect of inhibiting K(v)1.3 channels on DNA synthesis. rOsK-1 significantly inhibited the DNA synthesis induced by C5b-9 in OLG, indicating that K(v)1.3 plays an important role in the C5b-9-induced cell cycle. In addition, C5b-9-mediated myelin basic protein and proteolipid protein mRNA decay was completely abrogated by inhibition of K(v)1.3 expression. In the brains of multiple sclerosis patients, C5b-9 co-localized with NG2(+) OLG progenitor cells that expressed K(v)1.3 channels. Taken together, these data suggest that K(v)1.3 channels play an important role in controlling C5b-9-induced cell cycle activation and OLG dedifferentiation, both in vitro and in vivo.
authors.affiliation: Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Cosmin A
authors.initials: CA
authors.lastname: Tegla
authors.forename: Cornelia
authors.initials: C
authors.lastname: Cudrici
authors.forename: Monika
authors.initials: M
authors.lastname: Rozycka
authors.forename: Katerina
authors.initials: K
authors.lastname: Soloviova
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ito
authors.forename: Anil K
authors.initials: AK
authors.lastname: Singh
authors.forename: Aamer
authors.initials: A
authors.lastname: Khan
authors.forename: Philippe
authors.initials: P
authors.lastname: Azimzadeh
authors.forename: Maria
authors.initials: M
authors.lastname: Andrian-Albescu
authors.forename: Anver
authors.initials: A
authors.lastname: Khan
authors.forename: Florin
authors.initials: F
authors.lastname: Niculescu
authors.forename: Violeta
authors.initials: V
authors.lastname: Rus
authors.forename: Susan I V
authors.initials: SI
authors.lastname: Judge
authors.forename: Horea
authors.initials: H
authors.lastname: Rus
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D054337:Cell Dedifferentiation / Q000502:physiology*; D002478:Cells, Cultured; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000494:pharmacology
chemical_list: D015938:Complement Membrane Attack Complex; D051664:Kv1.3 Potassium Channel; C104504:OSK1 toxin, Orthochirus scrobiculosus; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms