Na-G is a putative sodium (or cationic) channel expressed in neurons and glia of the PNS, in restricted neuronal subpopulations of the brain, and in several tissues outside the nervous system, like lung and adrenal medulla. To analyze the mechanisms underlying tissuespecific expression of this channel, we isolated the 5Ј region of the corresponding gene and show that Na-G mRNA transcription proceeds from a single promoter with multiple initiation sites. By transgenic mice studies, we demonstrate that 600 bp containing the Na-G proximal promoter region and the first exon are sufficient to drive the expression of a ␤-galactosidase reporter gene in neurons of both CNS and PNS, whereas expression in Schwann cells depends on more remote DNA elements lying in the region between Ϫ6,500 and Ϫ1,050 bp upstream of the main transcription initiation sites. Crucial elements for lung-specific expression seem to be located in the region between Ϫ1,050 and Ϫ375 bp upstream of the promoter. Using in vivo footprint experiments, we demonstrate that several sites of the Na-G proximal promoter region are bound specifically by nuclear proteins in dorsal root ganglion neurons, as compared with nonexpressing hepatoma cells.

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 predominant brain and muscle fast voltage‐gated Na+ channels. In vivo, the corresponding 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 that Na‐G messenger RNA level in astrocyte and Schwann cell cultures is modulated in a cell‐specific manner by several growth factors, hormones, and intracellular second messengers pathways. Striking changes in transcript level were observed in the two types of glia in response to protein‐kinase A activation and to treatment with the neuregulin glial growth factor, indicating regulation of the Na‐G gene by neuroglial signaling. By transient transfection 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 high 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 sustain a low but reproducible transcriptional response to cAMP, accounting in part for the elevation in mRNA level elicited by cAMP in Schwann cells and its reduction in astrocytes. GLIA 33:230–240, 2001. © 2001 Wiley‐Liss, Inc.