Characterization of delayed rectifier Kv channels in oligodendrocytes and progenitor cells.
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.
Attali
B
B
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Wang
N
N
Kolot
A
A
Sobko
A
A
Cherepanov
V
V
Soliven
B
B
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D051668:Delayed Rectifier Potassium Channels; D006801:Humans; D017403:In Situ Hybridization; D017136:Ion Transport / Q000187:drug effects; D007668:Kidney; D051663:Kv1.2 Potassium Channel; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D046911:Macromolecular Substances; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology; D014162:Transfection
D051668:Delayed Rectifier Potassium Channels; C496969:KCNA2 protein, human; C496977:KCNA4 protein, human; C496981:KCNA5 protein, human; C496972:Kcna2 protein, rat; C496979:Kcna4 protein, rat; C496983:Kcna5 protein, rat; D051663:Kv1.2 Potassium Channel; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D019789:Tetraethylammonium; C022799:clofilium; D011803:Quinine; D015761:4-Aminopyridine; D011802:Quinidine; D011188:Potassium