The effect of mitochondrial inhibitors on calcium homeostasis in tumor mast cells
- Cornell Univ., Ithaca (USA)
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.
- OSTI ID:
- 6995015
- Journal Information:
- American Journal of Physiology; (USA), Vol. 258; ISSN 0002-9513
- Country of Publication:
- United States
- Language:
- English
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ANTIGENS
BIOLOGICAL FUNCTIONS
CALCIUM
MEMBRANE TRANSPORT
ANTIMYCIN
ATP
CALCIUM 45
ENZYME INHIBITORS
FLUORESCENCE
GLUCOSE
HOMEOSTASIS
LEUKEMIA
MAST CELLS
MITOCHONDRIA
RATS
SURVIVAL TIME
TRACER TECHNIQUES
TUMOR CELLS
ALDEHYDES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METALS
ANIMAL CELLS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CALCIUM ISOTOPES
CARBOHYDRATES
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELEMENTS
EVEN-ODD NUCLEI
FUNCTIONS
HEMIC DISEASES
HEXOSES
IMMUNE SYSTEM DISEASES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LUMINESCENCE
MAMMALS
METALS
MONOSACCHARIDES
NEOPLASMS
NUCLEI
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANOIDS
RADIOISOTOPES
RODENTS
SACCHARIDES
SOMATIC CELLS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques