Key result
K+ channel blockers inhibit oligodendrocyte progenitor proliferation, but isolated Kv1.5 or Kv1.6 antisense inhibition fails.
Delayed rectifier K+ currents in oligodendrocyte progenitor cells and differentiated oligodendrocytes are partly encoded by Kv1.5 subunits, but inhibiting Kv1.5 or Kv1.6 alone is insufficient to prevent mitogenesis.
Kv1.5 contributes to delayed rectifier currents in oligodendrocyte progenitors; leaves open redundant channel roles in proliferation control.
We examined the molecular identity of K+ channel genes underlying the delayed rectifier (IK) in differentiated cultured oligodendrocytes (OLGs) and oligodendrocyte progenitor (OP) cells. Using reverse transcription-PCR cloning, we found that OP cells and OLGs expressed multiple Kv transcripts, namely Kv1.2, Kv1.4, Kv.1.5, and Kv1.6. Immunocytochemical and Western blot analyses revealed that Kv1.5 and Kv1.6 as well as Kv1.2 and Kv1.4 channel proteins could be detected in these cells, but definitive evidence for functional K+ channel expression was obtained only for the Kv1.5 channel. In addition, mRNA and immunoreactive protein levels of both Kv1.5 and Kv1.6 channels were significantly lower in differentiated OLGs when compared with levels in OP cells. Proliferation of OP cells was inhibited by K+ channel blockers, but not by incubation with either Kv1.5 or Kv1.6 antisense oligonucleotides. We conclude that (1) IK in OP cells and OLGs is encoded partly by Kv1.5 subunits, possibly forming heteromultimeric channels with Kv1.6 or other Kv subunits; and (2) inhibition of Kv1.5 or Kv1.6 channel expression alone does not prevent mitogenesis. Concomitant inhibition of other Kv channels underlying IK may be necessary for OP cells to exit from cell cycle.
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Attali et al. (1997) studied this question. K+ channel blockers and antisense oligonucleotides vs. Untreated cells or sense oligonucleotides was evaluated on IK current density and cell proliferation. In cultured rat oligodendrocyte progenitor cells, delayed rectifier K+ currents are partly encoded by Kv1.5 subunits, and while K+ channel blockers inhibited cell proliferation, antisense inhibition of Kv1.5 or Kv1.6 alone did not.
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