RT Journal Article
SR Electronic
T1 Growth Factor-Induced Transcription of GluR1 Increases Functional AMPA Receptor Density in Glial Progenitor Cells
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 227
OP 240
DO 10.1523/JNEUROSCI.17-01-00227.1997
VO 17
IS 1
A1 Li-Jin Chew
A1 Mark W. Fleck
A1 Paul Wright
A1 Steven E. Scherer
A1 Mark L. Mayer
A1 Vittorio Gallo
YR 1997
UL http://www.jneurosci.org/content/17/1/227.abstract
AB We analyzed the effects of two growth factors that regulate oligodendrocyte progenitor (O-2A) development on the expression of glutamate receptor (GluR) subunits in cortical O-2A cells. In the absence of growth factors, GluR1 was the AMPA subunit mRNA expressed at the lowest relative level. Basic fibroblast growth factor (bFGF) caused an increase in GluR1 and GluR3 steady-state mRNA levels. Platelet-derived growth factor (PDGF) did not modify the mRNA levels for any of the AMPA subunits but selectively potentiated the effects of bFGF on GluR1 mRNA (4.5-fold increase). The kainate-preferring subunits GluR7, KA1, and KA2 mRNAs were increased by bFGF, but these effects were not modified by cotreatment with PDGF. Nuclear run-on assays demonstrated that PDGF+bFGF selectively increased the rate of GluR1 gene transcription (2.5-fold over control). Western blot analysis showed that GluR1 protein levels were increased selectively (sixfold over control) by PDGF+bFGF. Functional expression was assessed by rapid application of AMPA to cultured cells. AMPA receptor current densities (pA/pF) were increased nearly fivefold in cells treated with PDGF+bFGF, as compared with untreated cells. Further, AMPA receptor channels in cells treated with PDGF+bFGF were more sensitive to voltage-dependent block by intracellular polyamines, as expected from the robust and selective enhancement of GluR1 expression. Our combined molecular and electrophysiological findings indicate that AMPA receptor function can be regulated by growth factor-induced changes in the rate of gene transcription.