GROWTH FACTOR-INDUCED TRANSCRIPTION OF GLUR1 INCREASES FUNCTIONAL AMPA RECEPTOR DENSITY IN GLIAL PROGENITOR CELLS

We analyzed the effects of two growth factors that regulate oligodendr ocyte progenitor (O-2A) development on the expression of glutamate rec eptor (GluR) subunits in cortical O-2A cells. In the absence of growth factors, GluR1 was the AMPA subunit mRNA expressed at the lowest rela tive level. Basic fibroblast growth factor (bFGF) caused an increase i n GluR1 and GluR3 steady-state mRNA levels. Platelet-derived growth fa ctor (PDGF) did not modify the mRNA levels for any of the AMPA subunit s but selectively potentiated the effects of bFGF on GluR1 mRNA (4.5-f old increase). The kainate-preferring subunits GluR7, KA1, and KA2 mRN As were increased by bFGF, but these effects were not modified by cotr eatment with PDGF. Nuclear run-on assays demonstrated that PDGF+bFGF s electively increased the rate of GluR1 gene transcription (2.5-fold ov er control). Western blot analysis showed that GluR1 protein levels we re increased selectively (sixfold over control) by PDGF+bFGF. Function al expression was assessed by rapid application of AMPA to cultured ce lls. AMPA receptor current densities (pA/pF) were increased nearly fiv efold in cells treated with PDGF+bFGF, as compared with untreated cell s. Further, AMPA receptor channels in cells treated with PDGF+bFGF wer e more sensitive to voltage-dependent block by intracellular polyamine s, as expected from the robust and selective enhancement of GluR1 expr ession. Our combined molecular and electrophysiological findings indic ate that AMPA receptor function can be regulated by growth factor-indu ced changes in the rate of gene transcription.