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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2011; 57(1): 9-16

Mitochondrial Na+-Ca2+-exchanger inhibitor CGP37157 produces endothelial cell depolarization with membrane potential oscillations

Bondarenko OI, Sahach VF

    Bogomoletz Institute of physiology NAS of Ukraine, Kyiv, Ukraine


We explored the effect of inhibitor of mitochondrial Na+–Ca2+-exchanger CGP37157 and the effect of mitochondria perme­ability transition pore inhibitor, cyclosporine A, on the membrane potential and electrical responses to endothelium-dependent dilators in intact endothelial cells from excised rat aorta and EA.hy 926 endothelial cells. Cyclosporin A did not affect the resting membrane potential and hyperpolarization to acetylcholine and histamine in intact and cultured cells. In contrast, CGP37157 (20 mcM) evoked membrane depolariza­tion in unstimulated cells and suppressed the sustained component of hyperpolarization to acetylcholine and hista-mine both in intact and cultured endothelial cells, respectively. This was accompanied by a pronounced depolarization with membrane potential oscillations, which were not observed in the absence of Ca2+. We conclude that CGP37157 modulates endothelial membrane potential at rest and electrical responses to endothelium-dependent dilators. Possible mechanisms accompanying the CGP37157 action are discussed.

Keywords: endothelial cells, mitochondrial Na+–Ca2+-еxchanger, CGP37157, electrical responses


  1. Bondarenko OI, Sahach VF. Role of mitochondria in reglulation of endothelial cell hyperpolarization to acetylcholine.. Fiziol Zh. 2006;52(5):6-11. 
  3. Albert A.P. Large W.A. Store-operated Ca2+ permeable non-selective cation channels in smooth muscle cells . Cell Calcium. 2003. 33. P.345-356. CrossRef  
  4. Arnaudeau S., Kelley W.L., Jr Walsh J.V., Demaurex N., Mitochondria recycle Ca2+ to the endoplasmic reticulum and prevent the depletion of neighboring endoplasmic reticulum regions . J. Biol.Chem. 2001. 276. P.29430-29439. CrossRef PubMed
  6. Barbock D.F., Herrington J., Park Y-B., Hille B (1997). Mitichondria participation in the intracellular Ca2+ network . J. Cell Biol. 136. P.833-843. CrossRef PubMed PubMedCentral
  8. Bernardi P. Mitochondrial transport of cations: channels, exchangers and permeability transition . Physiol. Rev. 1999. 79. P.1127-1155. CrossRef PubMed
  10. Caputo C, Bolanos P. Effect of mitochondria poison-ing by FCCP on Ca2+ signaling in mouse skeletal muscle fibers . Pflug. Arch. 2008. 455(4). P.733-43. CrossRef PubMed
  12. Davidson. Duchen Endothelial mitochondria. Contri­buting to vascular funcrion and disease . Circulst. Res. 2007. 100. P.1128-1141. CrossRef PubMed
  14. Duszynski J., Koziel R., Brutkowski W., Szczepa-nowska J., Zablocki. The regulatory role of mitochon­dria in capacitative calcium entry . Biochim et Biophys Acta. 2006. 1757. P.380-387. CrossRef PubMed
  16. Freichel M., Suh S.H., Pfeifer A., Schweig U. Lack of an endothelial store-operfated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4-. mice . Nature Cell Biol. 2001. 3. P.121-127. CrossRef PubMed
  18. Malli R., Frieden M., Osibow K., Zoratti C, Mayer M., Demaurex N., Graier W. F. Sustained Ca2+ transfer across mitochondria is Essential for mitochondrial Ca2+ buffering, sore-operated Ca2+ entry, and Ca2+ store refilling . J. Biol Chem. 2003. 278. P.44769-44779. CrossRef PubMed
  20. Malli R., Frieden M., Trenker M., Graier W. F. The role of mitochondria for Ca2+ refilling of the endoplas­mic reticulum . Ibid. 2005. 280. 12114-12122. CrossRef PubMed
  22. Maruyama K, Ohta T, Ito S. Involvement of mito­chondrial Na+-Ca2+ exchange in intracellular Ca2+ in­crease induced by ATP in PC12 cells . Brain Res. 2004. 1013(1). P.40-50. CrossRef PubMed
  24. Nilius B., Droogmans G. Ion channels and their func­tional role in vascular endothelium . Physiol. Rev. 2001. 81. P.415-459. CrossRef PubMed
  26. Putney J.W., Broad L.M., Braun F. J. Mechanisms of capacitative calcium entry . J. Cell. Sci. 2001. 114. P.2223-2229.
  28. Rothberg B. S., Bello R. A., Song L., Magleby K. L. High Ca2+ concentrations induce a low activity mode and reveal Ca2+-independent long shut intervals in BK channels from rat muscle . J.Physiol. 1996. 493 (Pt 3). 673-689. CrossRef PubMed PubMedCentral
  30. Tracey W.R., Peach M.J. Differential muscarinic receptor mRNA expression by freshly isolated and cultured bovine endothelial cells . Circulat Res. 1992. 70. 234-240. CrossRef PubMed

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