Inhibition of voltage-dependent Na+ current in cell-fusion hybrids containing activated c-Ha-ras.

The electrophysiological properties of EJ (human bladder carcinoma), GM2291 (human fetal lung fibroblast), and of three hybrid cell lines obtained from their cell fusion were investigated using the patch-clamp technique. GM2291 cells, which are nontumorigenic, express voltage-dependent Na+ channels. The pharmacology and gating properties of the Na+ channels in GM2291 cells are distinct from neuronal and cardiac Na+ channels. EJ cells, which are tumorigenic and contain activated c-Ha-ras, express inward rectifier K+ channels. The three cell-fusion hybrid lines, named 145 (nontumorigenic), 145L (nontumorigenic but morphologically altered), and 147TR2 (fully tumorigenic segregant), have been previously shown to express levels of activated c-Ha-ras similar to those of the EJ parental line. Voltage-dependent Na+ channels were observed in none of the hybrid cell lines, while inward rectifier K+ channels were observed in each of the hybrid cell lines. The possibility that c-Ha-ras inhibits expression of a voltage-dependent Na+ channel is discussed.