title: Modulation of calcium fluxes in Jurkat T cells by myristic acid. Inhibition is independent of membrane potential and intracellular pH.
abstract: Treatment of T lymphocytes with mitogenic antibodies against the T-cell receptor/CD3 complex induces within seconds a rise in the concentration of intracellular free Ca2+. We recently reported that free myristic acid, but not its methyl ester, inhibits both the anti-CD3-induced Ca2+ influx across the cell membrane and the Ca2+ release from intracellular stores in Jurkat T cells. Here we show that myristic acid induced a rapid hyperpolarization of the cell membrane potential and a decrease in intracellular pH in Jurkat cells. Lauric acid and palmitic acid caused minor hyperpolarization, whereas other saturated non-esterified fatty acids tested were without effect. Hyperpolarization of the membrane potential in Jurkat cells with valinomycin did not, however, inhibit the anti-CD3-induced Ca2+ signal, and the blocking effect on the Ca2+ signal in myristic acid-treated Jurkat cells was not reversed after normalization of the cell membrane potential by treatment with gramicidin. The inhibitory effect of myristic acid on the Ca2+ fluxes thus cannot be explained by changes in membrane potential. We also present evidence that the blocking effect of myristic acid on the receptor-operated Ca2+ flux is not due to the myristic acid-induced decrease in intracellular pH. Moreover, we demonstrate that myristic acid does not prevent the release of Ca2+ triggered by inositol 1,4,5-trisphosphate from intracellular pools in permeabilized cells. Our findings indicate that myristic acid blocks anti-CD3-induced Ca2+ traffic in Jurkat cells by interfering with the regulation of Ca2+ mobilization, apparently by blocking an early step in signal transduction from the T-cell-antigen receptor/CD3 complex.
authors.affiliation: Department of Pathology, University of Helsinki, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Nordström
authors.forename: T
authors.initials: T
authors.lastname: Mustelin
authors.forename: T
authors.initials: T
authors.lastname: Pessa-Morikawa
authors.forename: L C
authors.initials: LC
authors.lastname: Andersson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007295:Inositol Phosphates; D007424:Intracellular Fluid / Q000378:metabolism; D007477:Ions; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016853:Muromonab-CD3 / Q000378:metabolism; D019814:Myristic Acid; D009227:Myristic Acids / Q000493:pharmacokinetics / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007295:Inositol Phosphates; D007477:Ions; D016853:Muromonab-CD3; D009227:Myristic Acids; D019814:Myristic Acid; D002118:Calcium