Somatostatin potentiates voltage-dependent K+ and Ca2+ channel expression induced by nerve growth factor in PC12 cells

Abstract

It has been proposed that neurotransmitters and neuromodulators may function as neurotrophic factors during the development of the nervous system. Somatostatin (SS) was known to increase neurite outgrowth in PC12 cells, rat pheochromocytoma cell line, and cerebellar granule cells as well as Helisoma neuron. To further investigate a neurotrophic role of SS, voltage-dependent K+ and Ca2+ channel expression was studied using whole-cell patch-clamp in PC12 cells and the effect of SS was compared to that of nerve growth factor (NGF). Cyclic AMP (cAMP) level and mitogen-activated protein (MAP) kinase phosphorylation were also studied following the treatment with SS and/or NGF. Whereas NGF (50 ng/ml) increased continually the current density of the voltage-dependent K+ channel throughout 8 days treatment, SS (1 microM) increased the K+ current density on day 2 to the peak. K+ current density was decreased thereafter and was not different on day 6 from that of undifferentiated cells. Although SS did not increase voltage-dependent Ca2+ current density, it potentiated NGF-induced increase of voltage-dependent Ca2+ channel current density as well as the K+ current density. cAMP level was decreased by NGF and/or SS treatment. An increased phosphorylation of MAP kinase induced by NGF was not changed by SS treatment. These results support functionally that SS may function as a neurotrophic factor in developing nervous system.