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

It has been proposed that neurotransmitters and neuromodulators may functio n as neurotrophic factors during the development of the nervous system. Som atostatin (SS) was known to increase neurite outgrowth in PC12 cells, rat p heochromocytoma cell line, and cerebellar granule cells as well as Helisoma neuron. To further investigate a neurotrophic role of SS, voltage-dependen t K+ and Ca2+ channel expression was studied using whole-cell patch-clamp i n PC12 cells and the effect of SS was compared to that of nerve growth fact or (NGF). Cyclic AMP (cAMP) level and mitogen-activated protein (MAP) kinas e phosphorylation were also studied following the treatment with SS and/or NGF. Whereas NGF (50 ng/ml) increased continually the current density of th e voltage-dependent K+ channel throughout 8 days treatment, SS (1 mu M) inc reased 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 undifferen tiated cells. Although SS did not increase voltage-dependent Ca2+ current d ensity, it potentiated NGF-induced increase of voltage-dependent Ca2+ chann el current density as well as the K+ current density, cAMP level was decrea sed by NGF and/or SS treatment. An increased phosphorylation of MAP kinase induced by NGF was not changed by SS treatment. These results support funct ionally that SS may function as a neurotrophic factor in developing nervous system. (C) 1999 Elsevier Science B.V. All rights reserved.