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Microprobe analysis of Tc-MIBI in heart cells: calculation of mitochondrial membrane potential.

Publication ,  Journal Article
Backus, M; Piwnica-Worms, D; Hockett, D; Kronauge, J; Lieberman, M; Ingram, P; LeFurgey, A
Published in: Am J Physiol
July 1993

Hexakis (2-methoxyisobutylisonitrile) technetium-99m (99mTc-MIBI) is a gamma-emitting radiopharmaceutical probe currently in clinical use to evaluate myocardial perfusion. Biochemical and cellular pharmacological studies have suggested that Tc-MIBI, a lipophilic cation, is sequestered in mitochondria in response to transmembrane potentials. To assess directly the subcellular distribution of the probe in heart tissue, cultured chick heart cells were analyzed by electron-probe X-ray microanalysis (EPXMA) following equilibration in micromolar concentrations of carrier-added 99Tc-MIBI, the ground-state radiopharmaceutical. Quantitation of the physiological elements Na, Ca, Mg, K, S, P, and Cl was correlated with exposure to increasing concentrations of 99Tc-MIBI. EPXMA signals indicated that 99Tc-MIBI was concentrated up to 1,000 times into mitochondria in a dose-dependent fashion based on measured Tc content in the mitochondria. Inner membrane potential (delta psi) of individual mitochondria was calculated as -117 mV using the Nernst equation. Concentrations of 99Tc-MIBI > 36 microM caused a significant efflux of K and Mg from the cell, as well as an increase in Cl in the mitochondria. Comparison of cell ultrastructure with conventional electron microscopy at extracellular 99Tc-MIBI concentrations of 36-72 microM showed no changes compared with control. 99Tc-MIBI allows valuable in situ investigation of cellular bioenergetics with EPXMA by quantitation of delta psi.

Duke Scholars

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

July 1993

Volume

265

Issue

1 Pt 1

Start / End Page

C178 / C187

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Technetium Tc 99m Sestamibi
  • Sulfur
  • Subcellular Fractions
  • Phosphorus
  • Myocardium
  • Mitochondria, Heart
  • Membrane Potentials
  • Electron Probe Microanalysis
  • Electrolytes
 

Citation

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Backus, M., Piwnica-Worms, D., Hockett, D., Kronauge, J., Lieberman, M., Ingram, P., & LeFurgey, A. (1993). Microprobe analysis of Tc-MIBI in heart cells: calculation of mitochondrial membrane potential. Am J Physiol, 265(1 Pt 1), C178–C187. https://doi.org/10.1152/ajpcell.1993.265.1.C178
Backus, M., D. Piwnica-Worms, D. Hockett, J. Kronauge, M. Lieberman, P. Ingram, and A. LeFurgey. “Microprobe analysis of Tc-MIBI in heart cells: calculation of mitochondrial membrane potential.Am J Physiol 265, no. 1 Pt 1 (July 1993): C178–87. https://doi.org/10.1152/ajpcell.1993.265.1.C178.
Backus M, Piwnica-Worms D, Hockett D, Kronauge J, Lieberman M, Ingram P, et al. Microprobe analysis of Tc-MIBI in heart cells: calculation of mitochondrial membrane potential. Am J Physiol. 1993 Jul;265(1 Pt 1):C178–87.
Backus, M., et al. “Microprobe analysis of Tc-MIBI in heart cells: calculation of mitochondrial membrane potential.Am J Physiol, vol. 265, no. 1 Pt 1, July 1993, pp. C178–87. Pubmed, doi:10.1152/ajpcell.1993.265.1.C178.
Backus M, Piwnica-Worms D, Hockett D, Kronauge J, Lieberman M, Ingram P, LeFurgey A. Microprobe analysis of Tc-MIBI in heart cells: calculation of mitochondrial membrane potential. Am J Physiol. 1993 Jul;265(1 Pt 1):C178–C187.

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

July 1993

Volume

265

Issue

1 Pt 1

Start / End Page

C178 / C187

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Technetium Tc 99m Sestamibi
  • Sulfur
  • Subcellular Fractions
  • Phosphorus
  • Myocardium
  • Mitochondria, Heart
  • Membrane Potentials
  • Electron Probe Microanalysis
  • Electrolytes