Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle.
Proliferative oligodendrocyte progenitor cells (OPs) express large, delayed outward-rectifying K(+) currents (I(K)), whereas nondividing immature and mature oligodendrocytes display much smaller I(K). Here, we show that up-regulation of I(K) occurs in G(1) phase of the cell cycle in purified cultured OPs and is the result of an RNA synthesis-dependent, selective increase of the K(+) channel subunit proteins Kv1.3 and Kv1.5. In oligodendrocyte cells acutely isolated from developing rat brain, a decrease of cyclin D expression is observed as these cells mature along their lineage. This is accompanied by a decrease in Kv1.3 and Kv1.5 subunit expression, suggesting a role for these subunits in the proliferative potential of OPs in situ. I(K) expressed in OPs in subventricular zone and developing white matter in acutely isolated slice preparations were selectively blocked by antagonists of Kv1.3, illustrating the functional presence of this subunit in situ. Interestingly, Kv1.3 block inhibited S-phase entry of both purified OPs in culture and in tissue slice cultures. Thus, we employ both in vitro and in situ experimental approaches to show that (i) RNA-dependent synthesis of Kv1.3 and Kv1.5 subunit proteins occurs in G(1) phase of the OP cell cycle and is responsible for the observed increase in I(K), and (ii) currents through Kv1.3-containing channels play a crucial role in G(1)/S transition of proliferating OPs.
Chittajallu
R
R
Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4495, USA.
Chen
Y
Y
Wang
H
H
Yuan
X
X
Ghiani
C A
CA
Heckman
T
T
McBain
C J
CJ
Gallo
V
V
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000378:metabolism / Q000502:physiology; D002455:Cell Division; D019070:Cell Lineage; D002478:Cells, Cultured; D056741:Cyclin D; D016213:Cyclins / Q000096:biosynthesis; D019281:Dimerization; D004594:Electrophysiology; D016193:G1 Phase; D006801:Humans; D007150:Immunohistochemistry; D051664:Kv1.3 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D015221:Potassium Channels / Q000096:biosynthesis*; D024642:Potassium Channels, Voltage-Gated; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016196:S Phase; D013997:Time Factors; D015854:Up-Regulation
D056741:Cyclin D; D016213:Cyclins; C496973:KCNA3 protein, human; C496981:KCNA5 protein, human; C496975:Kcna3 protein, rat; C496983:Kcna5 protein, rat; D051664:Kv1.3 Potassium Channel; D051666:Kv1.5 Potassium Channel; D010982:Platelet-Derived Growth Factor; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012313:RNA; C013411:biocytin; D008239:Lysine