Interleukin-1β inhibits Ca 2+ channel currents in hippocampal neurons through protein kinase C

Abstract

Interleukin-1β depresses the voltage-gated Ca 2+ channel currents in acutely dissociated guinea-pig hippocampal CA1 neurons. This depression is observed with pathophysiological concentrations found in the cerebrospinal fluid (≥ 1.0 pg interleukin-1 β/10 μl). Interleukin-1 receptor antagonist (in concentrations 25-fold higher than interleukin-1β) completely blocked the interleukin-1β-induced depression of the Ca 2+ channel current. This suggests that interleukin-1β 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-1β. The depression of the Ca 2+ channel current by interleukin-1β was prevented by the extracellular application of pertussis toxin, and by the intracellular application of GDP[βS], H-7, staurosporine or bisindolylmaleimide. Application of phorbol 12-myristate 13-acetate also depressed the Ca 2+ channel current, but this phorbol ester-induced depression was not additive to that induced by interleukin-1β. These results suggest mediation of interleukin-1β action through a pertussis toxin-sensitive G-protein coupled interleukin-1 receptor associated with the activation of protein kinase C. The depression of the Ca 2+ channel current by interleukin-1β may be involved in the regulation of neuronal excitability during pathological conditions and in the induction and/or progression of neurodegenerative processes.