Advertisement

Journal of Bioenergetics and Biomembranes

, Volume 19, Issue 5, pp 515–524 | Cite as

Inhibition of the Na+/Ca2+ antiport of heart mitochondria by diethylpyrocarbonate

  • Michael H. Davis
  • Dennis W. Jung
  • Gerald P. Brierley
Research Articles

Abstract

Diethylpyrocarbonate inhibits Na+/Ca2+ antiport activity in isolated heart mitochondria. The inhibition is time-dependent with maximum activity developed after 5 min at 25°C. The reaction of diethylpyrocarbonate with the mitochondrial membrane is biphasic with 25–30 nmol mg−1 reacting rapidly and an additional 30 nmol mg−1 taken up slowly over a 30-min incubation. Inhibition of mitochondrial Na+/Ca2+ antiport by diethylpyrocarbonate decreases theVmax of the reaction, and the inhibition cannot be reversed by washing the mitochondria or addition of excess histidine. The inhibition occurs at levels of inhibitor that have little or no effect on Ca2+ uptake, Na+/H+ antiport, or succinate respiration. A portion of the Na+-dependent efflux of Ca2+ is insensitive to diethylpyrocarbonate and this component is abolished by diltiazem. The mechanism by which diethylpyrocarbonate inactivates Na+/Ca2+ antiport is still uncertain, but may involve the modification of an unprotonated histidine residue in the transporter.

Key Words

Mitochondria diethylpyrocarbonate heart inhibition sodium calcium 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bindslev, N., and Wright, E. M. (1984).J. Membr. Biol. 81, 159–170.Google Scholar
  2. Brierley, G. P., and Jung, D. W. (1987). InRegulation of Cellular Ca 2+ Homeostasis (Fiskum, G., Little, L., McMillan-Wood, J. B., and Pfeiffers, D., eds.), Plenum Press, New York, in press.Google Scholar
  3. Brierley, G. P., Jurkowitz, M. S., Farooqui, T., and Jung, D. W. (1984).J. Biol. Chem. 259, 14672–14678.Google Scholar
  4. Crompton, M., and Heid, I. (1978).Eur. J. Biochem. 91, 599–608.Google Scholar
  5. Crompton, M., Capano, M., and Carafoli, E. (1976).Eur. J. Biochem. 69, 453–462.Google Scholar
  6. Crompton, M., Kunzi, M., and Carafoli, E. (1977).Eur. J. Biochem. 79, 549–558.Google Scholar
  7. Crompton, M., Moser, R., Ludi, H., and Carafoli, E. (1978).Eur. J. Biochem. 82, 25–31.Google Scholar
  8. Damiano, E., Bassilana, M., and Leblanc, G. (1985).Eur. J. Biochem. 148, 183–188.Google Scholar
  9. Grillo, F. G., and Aronson, P. S. (1986).J. Biol. Chem. 261, 1125–1125.Google Scholar
  10. Jacobus, W. E., and Brierley, G. P. (1969).J. Biol. Chem. 244, 4995–5004.Google Scholar
  11. Lundblod, R. L., and Noyes, C. M. (1984).Chemical Reagents for Protein Modification, Vol. I, CRC Press, Boca Raton, Florida, pp. 105–125.Google Scholar
  12. Matlib, M. A., and Schwartz, A. (1983).Life Sci. 32, 2837–2842.Google Scholar
  13. Melchoir, W. B., and Fahrney, D. (1970).Biochemistry 9, 251.Google Scholar
  14. Miles, E. W. (1977).Methods Enzymol. 47, 431–442.Google Scholar
  15. Nicholls, D. G., and Ackerman, K. (1982).Biochim. Biophys. Acta 683, 57–88.Google Scholar
  16. Ohkuma, S., and Poole, B. (1978).Proc. Natl. Acad. Sci. USA 75, 3327–3331.Google Scholar
  17. Rosen, B. P., and Futai, M. (1980).FEBS Lett. 117, 39–43.Google Scholar
  18. Rottenberg, H. (1979).Methods Enzymol. 55, 547–569.Google Scholar
  19. Vaghy, P. L., Johnson, J. D., Matlib, M. A., Wang, T., and Schwartz, A. (1982).J. Biol. Chem. 257, 6000–6002.Google Scholar

Copyright information

© Plenum Publishing Corporation 1987

Authors and Affiliations

  • Michael H. Davis
    • 1
  • Dennis W. Jung
    • 1
  • Gerald P. Brierley
    • 1
  1. 1.Department of Physiological ChemistryOhio State University Medical CenterColumbus

Personalised recommendations