Insulin and insulin-like growth factor-1 inhibit the L-type calcium channel current in rat pinealocytes

Tyrosine phosphorylation has recently been shown to modulate ion channel activity. In the present study, the effect of growth factors on the L-type Ca2+ channel current in rat pinealocytes was investigated using the whole version of the patch clamp technique. Both insulin and insulin-like growth factor-I (IGF-I) inhibited the L-type Ca2+ channel current. This inhibition was dependent on concentration, with median effective concentration (EC50) values of 60 nM for insulin and 0.14 nM for IGF-I. Heat-inactivated insulin or IGF-I had no effect on the L-type Ca2+ channel current. The presence of anti-IGF-I receptor antibodies blocked the inhibitory effect of IGF-I on the L-type Ca2+ channel current. Two other growth factors, nerve growth factor and epidermal growth factor? had no effect on this current. The effects of insulin and IGF-I were blocked by lavendustin A, a tyrosine kinase inhibitor. Calphostin C, a protein kinase C inhibitor, attenuated the effect of insulin and IGF-I, whereas wortmannin, a phosphatidylinositol 3-kinase inhibitor, was ineffective. These observations indicate that insulin and IGF-I inhibit the L-type Ca2+ channel current in rat pinealocytes, and that tyrosine phosphorylation is involved in these effects of insulin and IGF-I.