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.