Interleukin-1 beta inhibits Ca2+ channel currents in hippocampal neurons through protein kinase C

Eur J Pharmacol. 1994 Jan 1;266(1):1-10. doi: 10.1016/0922-4106(94)90202-x.


Interleukin-1 beta depresses the voltage-gated Ca2+ channel currents in acutely dissociated guinea-pig hippocampal CA1 neurons. This depression is observed with pathophysiological concentrations found in the cerebrospinal fluid (> or = 1.0 pg interluekin-1 beta/10 microliters). Interleukin-1 receptor antagonist (in concentrations 25-fold higher than interleukin-1 beta) completely blocked the interleukin-1 beta-induced depression of the Ca2+ channel current. This suggests that interleukin-1 beta action is through a specific interaction with an interleukin-1 membrane receptor site. The application of other cytokines and growth factors (interleukin-6, epidermal growth factor, and basic fibroblast growth factor), or bacterial lipopolysaccharide (endotoxin) had no effect, indicating specificity of action of interleukin-1 beta. The depression of the Ca2+ channel current by interleukin-1 beta was prevented by the extracellular application of pertussis toxin, and by the intracellular application of GDP[beta S], H-7, staurosporine or bisindolylmaleimide. Application of phorbol 12-myristate 13-acetate also depressed the Ca2+ channel current, but this phorbol ester-induced depression was not additive to that induced by interleukin-1 beta. These results suggest mediation of interleukin-1 beta action through a pertussis toxin-sensitive G-protein coupled interleukin-1 receptor associated with the activation of protein kinase C. The depression of the Ca2+ channel current by interleukin-1 beta may be involved in the regulation of neuronal excitability during pathological conditions and in the induction and/or progression of neurodegenerative processes.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Alkaloids / pharmacology
  • Animals
  • Calcium Channels / drug effects*
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • GTP-Binding Proteins / metabolism
  • Guanosine Diphosphate / pharmacology
  • Guinea Pigs
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / enzymology
  • Interleukin-1 / pharmacology*
  • Isoquinolines / pharmacology
  • Neurons / drug effects*
  • Pertussis Toxin
  • Piperazines / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Staurosporine
  • Tetradecanoylphorbol Acetate / pharmacology
  • Virulence Factors, Bordetella / pharmacology


  • Alkaloids
  • Calcium Channels
  • Interleukin-1
  • Isoquinolines
  • Piperazines
  • Virulence Factors, Bordetella
  • Guanosine Diphosphate
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Pertussis Toxin
  • Protein Kinase C
  • GTP-Binding Proteins
  • Staurosporine
  • Tetradecanoylphorbol Acetate