Clonal sublines of rat neurotumor RT4 and cell differentiation. V. Comparison of Na+ influx, Rb+ efflux, and action potential among stem-cell, neuronal, and glial cell types.

A multipotential stem-cell-type cell line (RT4-AC) isolated from a rat peripheral neurotumor differentiates in culture into two neuronal-type cells (RT4-B and RT4-E) or into a glial-type cell (RT4-D). The neuronal classification of RT4-B and RT4-E cells is based on their positive response to veratridine in the tetrodotoxin-sensitive Na+-influx and Rb+-efflux assays and on the action potential observed upon hyperpolarized stimulation. In addition, these neuronal cell types do not synthesize two glial proteins, S100 protein (S100P) and glial fibrillary acidic protein (GFAP). The glial classification of RT4-D is based on the syntheses of S100P and GFAP. Additionally, RT4-D does not display veratridine-activated Na+ influx and Rb+ efflux nor action potential. The stem cell type, RT4-AC, expresses both neuronal and glial properties to a lesser degree. In the neuronal-type cell lines of the RT4 family (RT4-B and RT4-E), the large veratridine-activated Na+ influx can further be stimulated by scorpion toxin. The Na+ influx of the stem cell (RT4-AC), however, is only slightly stimulated by veratridine alone, but greatly stimulated by the addition of veratridine and scorpion toxin. These observations suggest that a progressive differentiation of voltage-dependent Na+ channels may have occurred by the cell-type conversion from the stem cell type to the neuronal cell types. The exact nature of the change in Na+ channels is currently not known.