Insulin-like growth factor I modulates voltage-dependent Ca2+ channels in neuronal cells.
Insulin and insulin-like growth factors are neuroactive peptides. We investigated the effect of insulin-like growth factor I (IGF-I) on Ca2+ channel currents in 108CC15 neuroblastoma x glioma (N x G) cells and a possible role of protein kinase C (PKC). Whereas the native IGF-I enhanced the Ca2+ channel current density in N x G cells, the boiled IGF-I had no effect. The effect of IGF-I occurred after 1-2 h incubation and reversed within 24 h. Ca2+ channel currents recorded in control cells were mainly of a low-threshold fast inactivating type and showed a mean density of 5.9 +/- 0.3 pA/pF. Current density in cells incubated with IGF-I (0.2 micrograms/ml) for 2 h increased to 9.2 +/- 0.8 pA/pF. Ca2+ channel currents in cells treated with IGF-I showed an enhanced amount of a high-threshold slowly inactivating Ca2+ current type sensitive to the dihydropyridine isradipine and the snail toxin omega-conotoxin. The effect of IGF-I was suppressed by coincubation with the PKC inhibitors 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7) and staurosporin which were both without effect on current density in control cells. Whereas the inactive phorbol ester phorbol 12-myristate 13-acetate (PMA) failed to modulate Ca2+ channels in N x G cells, stimulation of PKC by the active phorbol ester PMA mimicked the effect of IGF-I. The effects of IGF-I and phorbol ester were not additive. Our data suggest an intracellular mechanism dependent on PKC and we propose a physiological relevance of the observed Ca2+ channel modulation by IGF-I in the neuroactivity of the peptide.
Kleppisch
T
T
Institut für Physiologie, Humboldt-Universität zu Berlin, FRG.
Klinz
F J
FJ
Hescheler
J
J
D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004594:Electrophysiology; D006825:Hybridomas / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D017275:Isradipine / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; D007334:Insulin-Like Growth Factor I; D011493:Protein Kinase C; D017275:Isradipine