Insulin-like growth factor I modulates voltage-dependent Ca2+ channels in neuronal cells

Thomas Kleppisch, Franz Josef Klinz, Jürgen Hescheler

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31 Scopus citations


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 × glioma (N × G) cells and a possible role of protein kinase C (PKC). Whereas the native IGF-I enhanced the Ca2+ channel current density in N × 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 μg/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 ω-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 × 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.

Original languageEnglish
Pages (from-to)283-288
Number of pages6
JournalBrain Research
Issue number2
StatePublished - 25 Sep 1992
Externally publishedYes


  • 1,4-Dihydropyridine
  • Ca channel
  • Insulin-like growth factor I
  • Neuroblastoma × glioma cell line
  • Protein kinase C
  • ω-Conotoxin


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