INSULIN-LIKE GROWTH-FACTOR-I INDUCES A RAPID INCREASE IN CALCIUM CURRENTS AND SPONTANEOUS MEMBRANE-ACTIVITY IN CLONAL PITUITARY-CELLS

The role of growth factors in the adult brain is largely unknown, alth ough receptors for factors such as insulin-like growth factor-I (IGF-I ) have been localized on nondividing mature neurons. Because neurons u se the frequency and pattern of action potentials to encode informatio n, we assessed the ability of IGF-I to modulate rapidly the electrical properties of GH(4)C(1) cells, a spontaneously active pituitary line with neuronal L- and T-type calcium currents. Electrical quiescence (t he absence of spontaneous activity) was induced by culture in serum-de pleted conditions. IGF-I, which is synthesized locally in mammalian br ain, induced a rapid increase in electrical activity that was accompan ied by increased activation of calcium channel currents. These effects were dose and time dependent. The spontaneous activity of cells expos ed to 20 ng/ml IGF-I increased in similar to 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 spontane ous 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.