Segregation of Na(+)-channel gene expression during neuronal-glial branching of a rat PNS-derived stem cell line, RT4-AC.

RT4 is a family of cell lines isolated from an ethylnitrosourea-induced rat peripheral neurotumor. RT4-AC cells express both excitable membrane and glial cell properties. In a process called cell-type conversion, RT4-AC cells segregate these properties to generate three distinct derivative cell types which have been classified as either neuronal (RT4-E and RT4-B) or glial (RT4-D). In this report we demonstrate that: (1) upon cell-type conversion, Na(+)-channel mRNA expression segregates primarily with the RT4 neuronal derivatives, (2) the SkM2 Na(+)-channel gene, which was originally isolated from rat muscle cDNA libraries, is the predominant gene expressed by the RT4 neuronal derivatives, (3) the three rat brain Na(+)-channel genes I, II, and III and the muscle-derived SkM1 gene are not the principal Na(+)-channel genes involved in the segregation, although very low levels of message of these genes are detected, and (4) the RT4 glial derivative expresses slightly higher levels of message from rat brain genes I and II than the neuronal derivatives. Since the RT4 cell lines were derived from a peripheral neurotumor these results present the possibility that the SkM2 gene may be important in vivo in the rat peripheral nervous system.