Genetic and epigenetic control of the Na-G ion channel expression in glia

The Na-G ion channel, previously cloned from a rat astroglia cDNA library, belongs to a new family of ion channels, related to but distinct from the p redominant brain and muscle fast voltage-gated Naf channels. In vivo, the c orresponding transcripts are widely expressed in peripheral nervous system neurons and glia, but only in selected subpopulations of neuronal and glia- like cells of the central nervous system. In the present report, we show th at Na-G messenger RNA level in astrocyte and Schwann cell cultures is modul ated in a cell-specific manner by several growth factors, hormones, and int racellular second messengers pathways. Striking changes in transcript level were observed in the two types of glia in response to protein-kinase A act ivation and to treatment with the neuregulin glial growth factor, indicatin g regulation of the Na-G gene by neuroglial signaling. By transient transfe ction of Na-G/reporter constructs into cultured cells, we show that a short genomic region, encompassing the first exon and 375 bp upstream, bears a h igh glial-specific transcriptional activity while part of the first intron behaves as a negative regulatory element. In vivo footprinting experiments revealed binding of glial-specific nuclear factors to several sites of the Na-G promoter region. Finally, Na-G/reporter constructs are shown to sustai n a low but reproducible transcriptional response to cAMP, accounting in pa rt for the elevation in mRNA level elicited by cAMP in Schwann cells and it s reduction in astrocytes. (C) 2001 Wiley-Liss, Inc.