RT Journal Article SR Electronic T1 K+ Channel Expression and Cell Proliferation Are Regulated by Intracellular Sodium and Membrane Depolarization in Oligodendrocyte Progenitor Cells JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 2669 OP 2682 DO 10.1523/JNEUROSCI.17-08-02669.1997 VO 17 IS 8 A1 Peter Knutson A1 Cristina A. Ghiani A1 Jia-Min Zhou A1 Vittorio Gallo A1 Chris J. McBain YR 1997 UL http://www.jneurosci.org/content/17/8/2669.abstract AB The effects of a variety of antiproliferative agents on voltage-dependent K+ channel function in cortical oligodendrocyte progenitor (O-2A) cells were studied. Previously, we had shown that glutamate receptor activation reversibly inhibited O-2A cell proliferation stimulated by mitogenic factors and prevented lineage progression by attenuating outward K+ currents in O-2A cells. We now show that the antiproliferative actions of glutamate receptor activation are Ca2+-independent and arise from an increase in intracellular Na+ and subsequent block of outward K+ currents. In support of this mechanism, agents that acted to depolarize O-2A cells or increase intracellular sodium similarly had an antiproliferative effect, attributable at least in part to a reduction in voltage-gated K+ currents. Also, these effects were reversible and Ca2+-independent. Chronic treatment with glutamate agonists was without any long-term effect on K+ current function. Cells cultured in elevated K+, however, demonstrated an upregulation of inward rectifier K+ currents, concomitant with an hyperpolarization of the resting membrane potential. This culture condition therefore promoted a current phenotype typical of pro-oligodendroblasts. Finally, cells chronically treated with the mitotic inhibitor retinoic acid displayed a selective downregulation of outward K+ currents. In conclusion, signals that affect O-2A cell proliferation do so by regulating K+ channel function. These data indicate that the regulation of K+currents in cells of the oligodendrocyte lineage plays an important role in determining their proliferative potential and demonstrate that O-2A cell K+ current phenotype can be modified by long-term depolarization of the cell membrane.