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. 1993 Nov 1;295(Pt 3):773–779. doi: 10.1042/bj2950773

Complement-induced Ca2+ influx in cultured fibroblasts is decreased by the calcium-channel antagonist nifedipine or by some bivalent inorganic cations.

P Newsholme 1, A A Adogu 1, M A Soos 1, C N Hales 1
PMCID: PMC1134628  PMID: 8240291

Abstract

The effects of different extracellular cations or organic Ca(2+)-channel modulators on complement-induced changes in intracellular Ca2+ and cell death have been investigated in the transfected NIH-3T3 HIR 3.5 cell line, which overexpresses the human insulin receptor. Cells were incubated with mouse anti-(human insulin receptor) monoclonal antibodies before exposure to rabbit or human serum (sources of heterologous complement). Changes in intracellular Ca2+ were complement-dependent (measured by influx of 45Ca), as was cytotoxicity (monitored by leakage of lactate dehydrogenase into the culture supernatant). Addition of a dihydropyridine Ca(2+)-channel antagonist (nifedipine) or some bivalent inorganic cations caused inhibition of 45Ca entry via a novel channel distinct from endogenous voltage-gated Ca2+ channels. Nifedipine decreased, but conversely the addition of a phenylalkylamine Ca(2+)-channel antagonist (verapamil) or the inorganic Ca2+ agonists Ba2+ and Sr+ increased, complement-induced cytotoxicity. These agents had no effect on cell viability at the studied concentrations, in the absence of complement. It is concluded that complement-induced cytotoxicity is mediated by Ca2+ influx through novel specific transmembrane channels which are sensitive to the Ca(2+)-channel antagonist nifedipine, but otherwise show little resemblance to L- or T-type voltage-gated Ca2+ channels.

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Selected References

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