Interleukin-1β, tumor necrosis factor-α, and LPS enhance calcium channel current in isolated vascular smooth muscle cells of rat tail artery

M. F. Wilkinson, M. L. Earle, Christopher Triggle, S. Barnes

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Abstract

Cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), are thought to be responsible for the compromised blood pressure regulation after systemic infection or other antigenic challenge. Because Ca homeostasis is critical for the maintenance of vascular tone, we hypothesized that cytokines may contribute to alterations in blood pressure by a mechanism involving the voltage-sensitive Ca channel in vascular smooth muscle (VSM) cells. Using nystatin-permeabilized patch techniques we examined the effects of IL-1β, TNF-α, and lipopolysaccharide (LPS) on the Ca channel of VSM cells isolated from rat tail artery. Both IL-1β (0.05-1 nM) and TNF-α (0.1- 1 nM) increased, dose-dependently, the Ba2+ current carried in VSM Ca channels, whereas heat-denatured IL-1β was without significant effect on the channel. LPS (0.01-1.0 ng/ml) also increased the Ba2+ current with onset kinetics similar to the two cytokines. Prostaglandins were ruled out as an intermediary in VSM Ca channel modulation, as prostaglandin E2 had no effect and indomethacin (1 μM) failed to block TNF-α-induced Ca channel enhancement. The role of cyclic nucleotides in mediating TNF-α-induced changes in Ca channel activity was also assessed. Increasing intracellular cAMP via forskolin (1 μM) did not affect the response to TNF-α, but pretreatment with the membrane-permeant analog of cGMP, dibutyryl cGMP (100 μM), inhibited the response to TNF-α. These data demonstrate that IL-1β, TNF-α, and LPS have immediate effects on VSM cells via an interaction with the voltage-sensitive Ca channel, and these effects may be regulated by intracellular cGMP. Immunomodulation of Ca channels may represent an early signaling step in VSM cells mediating kinetically slower events, such as changes in gene transcription.

Original languageEnglish
Pages (from-to)785-791
Number of pages7
JournalFASEB Journal
Volume10
Issue number7
Publication statusPublished - May 1996
Externally publishedYes

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Keywords

  • calcium channel
  • cytokine
  • endotoxin
  • immunomodulation
  • patch clamp

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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