The effect of mitochondrial inhibitors on calcium homeostasis in tumor mast cells

Frederick C Mohr, C. Fewtrell

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The depletion of intracellular ATP by mitochondrial inhibitors in a glucose-free saline solution inhibited antigen-stimulated 45Ca uptake, the rise in cytoplasmic calcium, measured by fura-2, and secretion in rat basophilic leukemia cells. Lowering the intracellular ATP concentration also released calcium from an intracellular store and made further 45Ca efflux from the cells unresponsive to subsequent antigen stimulation. Antigen-stimulated 45Ca efflux could be restored by the addition of glucose. The ATP-sensitive calcium store appeared to be the same store that releases calcium in response to antigen. In contrast, intracellular ATP was not lowered, and antigen-stimulated secretion was unaffected by mitochondrial inhibitors, provided that glucose was present in the bathing solution. Similarly, antigen-stimulated 45Ca uptake, 45Ca efflux, and the rise in free ionized calcium were unaffected by individual mitochondrial inhibitors in the presence of glucose. However, when the respiratory chain inhibitor antimycin A was used in combination with the ATP synthetase inhibitor oligomycin in the presence of glucose, antigen-stimulated 45Ca uptake was inhibited, whereas the rise in free ionized calcium and secretion were unaffected. Also, antigen-induced depolarization (an indirect measurement of Ca2+ influx across the plasma membrane) was not affected. The inhibition of antigen-stimulated 45Ca uptake could, however, be overcome if a high concentration of the Ca2+ buffer quin2 was present in the cells to buffer the incoming 45Ca. These results suggest that in fully functional rat basophilic leukemia cells the majority of the calcium entering in response to antigen stimulation is initially buffered by a calcium store sensitive to antimycin A and oligomycin, presumably the mitochondria.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume258
Issue number2 27-2
StatePublished - 1990
Externally publishedYes

Fingerprint

Mast Cells
Tumors
Homeostasis
Calcium
Antigens
Neoplasms
Adenosine Triphosphate
Glucose
Antimycin A
Oligomycins
Rats
Buffers
Leukemia
Mitochondria
Fura-2
Depolarization
Cell membranes
Ligases
Electron Transport
Sodium Chloride

Keywords

  • intracellular calcium stores
  • rat basophilic leukemia cells
  • secretion

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

The effect of mitochondrial inhibitors on calcium homeostasis in tumor mast cells. / Mohr, Frederick C; Fewtrell, C.

In: American Journal of Physiology - Cell Physiology, Vol. 258, No. 2 27-2, 1990.

Research output: Contribution to journalArticle

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