Insulin-like growth factor-I induces a rapid increase in calcium currents and spontaneous membrane activity in clonal...

The role of growth factors in the adult brain is largely unknown, although receptors for factors such as insulin-like growth factor-I (IGF-I) have been localized on nondividing mature neurons. Because neurons use the frequency and pattern of action potentials to encode information, we assessed the ability of IGF-I to modulate rapidly the electrical properties of GH4C1 cells, a spontaneously active pituitary line with neuronal L- and T-type calcium currents. Electrical quiescence (the absence of spontaneous activity) was induced by culture in serum-depleted conditions. IGF-I, which is synthesized locally in mammalian brain, induced a rapid increase in electrical activity that was accompanied by increased activation of calcium channel currents. These effects were dose and time dependent. The spontaneous activity of cells exposed to 20 ng/ml IGF-I increased in approximately 10 sec and, after a brief exposure, continued increasing for at least 8 hr. Currents carried by calcium channels doubled within 10 sec. Both the increase in spontaneous activity and the increased activation of calcium channel currents were blocked by tyrosine kinase inhibitors. These results suggest that IGF-I can act as a rapid neuromodulator of calcium currents.