RAS-INDEPENDENT INDUCTION OF RAT-BRAIN TYPE-II SODIUM-CHANNEL EXPRESSION IN NERVE GROWTH FACTOR-TREATED PC12-CELLS

Nerve growth factor (NGF) plays an important role in the development of the nervous system, and there is considerable interest in understanding the molecular mechanisms underlying its effects on neuronal differentiation. To determine if the activity of proteins of the ras gene family is necessary for the NGF-mediated induction of sodium channel expression in pheochromocytoma (PC12) cells, sodium channel expression was analyzed in PC12 sublines stably overexpressing the dominant inhibitory mutant c-Ha-ras(Asn-17). Northern blot analysis, RNase protection assays, and whole-cell patch clamp recordings indicate that the NGF-mediated increase in type 11 sodium channel mRNA and sodium current density can occur independent of ras activity and by doing so provide strong evidence for the importance of ras-independent mechanisms in NGF-mediated neuronal differentiation.