Oligodendrocyte progenitor cell proliferation and lineage progression are regulated by glutamate receptor-mediated K+ channel block

V. Gallo,Jia Min Zhou,C. McBain,P. Wright,P. Knutson,R. Armstrong

Published 1996 in Journal of Neuroscience

ABSTRACT

We have analyzed the role of glutamate and its receptors (GluRs) in regulating the development of oligodendrocytes. Activation of AMPA- preferring GluRs with selective agonists inhibited proliferation of purified cortical oligodendrocyte progenitor (O-2A) cells cultured with different mitogens, as measured by [3H]thymidine incorporation or bromodeoxyuridine staining. In contrast, activation of GABA or muscarinic receptors did not affect O-2A proliferation. Cell viability and apoptosis assays demonstrated that the inhibition of O-2A proliferation was not attributable to a cytotoxic action of GluR agonists, and was reversible. Activation of GluRs prevented lineage progression from the O-2A (GD3+/nestin+) stage to the prooligodendroblast (O4+) stage, but did not affect O-2A migration. Additional experiments examined the membrane ionic channels mediating these GluR activation effects. We found that proliferating O-2A cells expressed functional delayed rectifier K+ channels, which were absent in pro-oligodendroblasts. GluR agonists and the K+ channel blocker tetraethylammonium (TEA) strongly inhibited delayed rectifier K+ currents in O-2A cells. TEA reproduced the effects of GluR activation on O-2A proliferation and lineage progression in the same concentration range that blocked delayed rectifier K+ currents. These results indicate that glutamate regulates oligodendrogenesis specifically at the O-2A stage by modulating K+ channel activity.

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