The technique of ion microscopy will be applied to a number of biomedical problems for the study of intracellular localization of elemental distribution and ion transport. Much of the proposed research depends on the unique isotopic imaging capability of the ion microscope, and represents the culmination of our continued efforts to demonstrate the problem solving capabilities of ion microscopy in biology and medicine. Stable isotopes of calcium and magnesium will be used in conjunction with cryosample preparation methodologies for understanding a number of fundamental and applied collaborative biomedical problems. Enriched stable (44)Ca and (26)Mg isotopes will be used to study the basic phenomenon of cellular calcium and magnesium exchange at the subcellular level in tissue culture cells. In collaboration with researchers at Cornell, the ion microscope will be used to understand intestinal, calcium absorption using (44)Ca as a tracer for calcium transport. (44)Ca will also be used to investigate the complex role of calcium in the secretory response of mast cells during the allergic reaction. In another collaborative biomedical study, the multielement imaging capability of the ion microscope will be used to screen neuronal populations for the existence of functional neurotransmitter receptors. A successful completion of this program would not only provide important new information regarding the proposed biomedical studies, but also establish ion microscopy as an essential technique in many subcellular ion transport related studies previously unattainable.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM024314-16
Application #
3272204
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1977-07-01
Project End
1993-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
16
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Chandra, Subhash (2005) Quantitative imaging of subcellular calcium stores in mammalian LLC-PK1 epithelial cells undergoing mitosis by SIMS ion microscopy. Eur J Cell Biol 84:783-97
Chandra, S; Leinhos, G M; Morrison, G H et al. (1999) Imaging of total calcium in urediospore germlings of Uromyces by ion microscopy. Fungal Genet Biol 27:77-87
Chandra, S; Morrison, G H; Beyenbach, K W (1997) Identification of Mg-transporting renal tubules and cells by ion microscopy imaging of stable isotopes. Am J Physiol 273:F939-48
Chandra, S; Morrison, G H (1997) Evaluation of 26Mg stable isotope as an in vivo tracer of magnesium transport for SIMS ion microscopy imaging studies. J Microsc 188:182-90
Chandra, S; Morrison, G H (1997) Evaluation of fracture planes and cell morphology in complementary fractures of cultured cells in the frozen-hydrated state by field-emission secondary electron microscopy: feasibility for ion localization and fluorescence imaging studies. J Microsc 186:232-45
Fullmer, C S; Chandra, S; Smith, C A et al. (1996) Ion microscopic imaging of calcium during 1,25-dihydroxyvitamin D-mediated intestinal absorption. Histochem Cell Biol 106:215-22
Wasserman, R H; Fullmer, C S (1995) Vitamin D and intestinal calcium transport: facts, speculations and hypotheses. J Nutr 125:1971S-1979S
Zha, X; Chandra, S; Ridsdale, A J et al. (1995) Golgi apparatus is involved in intracellular Ca2+ regulation in epithelial LLC-PK1 cells. Am J Physiol 268:C1133-40
Zha, X; Morrison, G H (1995) Ion microscopy evidence that La3+ releases Ca2+ from Golgi complex in LLC-PK1 cells. Am J Physiol 269:C923-8
Chandra, S; Fewtrell, C; Millard, P J et al. (1994) Imaging of total intracellular calcium and calcium influx and efflux in individual resting and stimulated tumor mast cells using ion microscopy. J Biol Chem 269:15186-94

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