C5b-9-activated, K(v)1.3 channels mediate oligodendrocyte cell cycle activation and dedifferentiation

Exp Mol Pathol. 2011 Aug;91(1):335-45. doi: 10.1016/j.yexmp.2011.04.006. Epub 2011 Apr 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Cycle / drug effects
  • Cell Cycle / physiology*
  • Cell Dedifferentiation / physiology*
  • Cells, Cultured
  • Complement Membrane Attack Complex / physiology*
  • Humans
  • Kv1.3 Potassium Channel / metabolism*
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / pathology
  • Oligodendroglia / cytology*
  • Oligodendroglia / drug effects
  • Oligodendroglia / physiology
  • Potassium Channel Blockers / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Scorpion Venoms / pharmacology


  • Complement Membrane Attack Complex
  • Kv1.3 Potassium Channel
  • OSK1 toxin, Orthochirus scrobiculosus
  • Potassium Channel Blockers
  • Scorpion Venoms