Effect of the sulfhydryl reagent thimerosal on cytosolic free Ca2+ and membrane potential of thymocytes

Biochim Biophys Acta. 1992 Oct 19;1111(1):65-74. doi: 10.1016/0005-2736(92)90275-q.

Abstract

The sulfhydryl reagent thimerosal at concentrations 5-100 microM has been found to induce a variety of changes in ion transport in rat thymocytes. In particular, [Ca2+]i increases about 10-fold from the basal level. The [Ca2+]i response to thimerosal displays a two-stage time course, with the main [Ca2+]i rise during the second stage. Evidence has been obtained for the depletion of intracellular Ca2+ pools in thimerosal-treated cells, however, Ca2+ mobilization from intracellular stores does not contribute significantly into [Ca2+]i rise. Thimerosal elicits permeability not only for Ca2+, but also for Mn2+ and Ni2+, which is Ca(2+)-dependent. We failed to get any evidence on thimerosal-induced inhibition of the plasma membrane Ca(2+)-ATPase. The induction of Ca2+ influx, rather than inhibition of Ca(2+)-ATPase, accounts for the disturbance of [Ca2+]i homeostasis in thimerosal-treated cells. Thimerosal also elicits changes in monovalent ion fluxes resulting in marked depolarization. The latter seems unrelated to the changes in [Ca2+]i and is suggested to be mediated both by increased permeability for Na+ and a decreased one for K+. Thimerosal significantly stimulates AA release from thymocytes. Evidence has been presented that AA metabolite(s), probably, LO product(s), may mediate the changes in the transport of mono- and divalent cations elicited by the sulfhydryl reagent. Prolonged treatment of thymocytes with thimerosal resulted in cell death.

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • Arachidonic Acid / pharmacology
  • Calcium / metabolism*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytosol / metabolism*
  • Hydroxyeicosatetraenoic Acids / pharmacology
  • Ion Transport / drug effects
  • Manganese / metabolism
  • Membrane Potentials / drug effects
  • Nickel / metabolism
  • Rats
  • Rats, Wistar
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Thimerosal / pharmacology*

Substances

  • Hydroxyeicosatetraenoic Acids
  • Thimerosal
  • Arachidonic Acid
  • Manganese
  • 5-hydroxy-6,8,11,14-eicosatetraenoic acid
  • Nickel
  • Calcium