Trypanosoma cruzi: Mechanisms of intracellular calcium homeostasis

Helieh S. Oz, Murray Wittner, Herbert B. Tanowitz, John P. Bilezikian, Maya Saxon, Stephen A. Morris

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Abstract

Regulation of intracellular Ca2+ homeostasis was characterized in epimastigote forms of Trypanosoma cruzi using the fluorescence probe Fura-2. Despite an increase in extracellular Ca2 +, [Ca2 +]o, from 0 to 2 mM, cytosolic Ca2+, [Ca2+]i, increased only from 85 ± 9 to 185 ± 21 nM, indicating the presence of highly efficient mechanisms for maintaining [Ca2+]i. Exposure to monovalent Na+ (monensin)-, K+ (valinomycin, nigericin)-, and divalent Ca2+ (ionomycin)-specific ionophores, uncouplers of mitochondrial respiration (oligomycin), inhibitors of Na+/K+-ATPase (ouabain), and Ca2+-sensitive ATPase (orthovanadate) in 0 or 1 mM [Ca2+ ]o resulted in perturbations of [Ca2+]i, the patterns of which suggested both sequestration and extrusion mechanisms. Following equilibration in 1 mM [Ca2+]o, incubation with orthovanadate markedly increased [Ca2+]i, results which are compatible with an active uptake of [Ca2+]i by endoplasmic reticulum. In contrast, equilibration in 0 or 1 mM [Ca2+]o did not influence the relatively smaller increase in [Ca2+]i following incubation with oligomycin, suggesting a minor role for the mitochondrial compartment. In cells previously equilibrated in 1 mM [Ca2+]o, exposure to monensin or ouabain, conditions known to decrease the [ Na+]o [Na+]i gradient, upon which the Na+ Ca2+ exchange pathways are dependent, markedly increased [Ca2+]i. In a complementary manner, decreasing the extracellular Na+ gradient with Li+ increased [Ca2+]i in a dose-dependent manner. Finally, the calcium channel blockers verapamil and isradipine inhibited the uptake of Ca2+ by greater than 50%, whereas diltiazem, nifedipine, and nicardipine were ineffective. The results suggest that epimastigote forms of T. cruzi maintain [Ca2+]i by uptake, sequestration, and extrusion mechanisms, with properties common to eukaryotic organisms.

Original languageEnglish (US)
Pages (from-to)390-399
Number of pages10
JournalExperimental Parasitology
Volume74
Issue number4
DOIs
StatePublished - Jun 1992

Keywords

  • Trypanosoma cruzi
  • calcium ionophores
  • intracellular calcium homeostasis

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

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    Oz, H. S., Wittner, M., Tanowitz, H. B., Bilezikian, J. P., Saxon, M., & Morris, S. A. (1992). Trypanosoma cruzi: Mechanisms of intracellular calcium homeostasis. Experimental Parasitology, 74(4), 390-399. https://doi.org/10.1016/0014-4894(92)90201-K