Ukr.Biochem.J. 2020; Volume 92, Issue 1, Jan-Feb, pp. 41-55

doi: https://doi.org/10.15407/ubj92.01.041

Influence of Tl(+) on the Ca(2+) and Na(+) movement across rat neonatal cardiomyocytes and rat heart mitochondria membranes

03.02.2020   Uncategorized   No comments

S. M. Korotkov, V. P. Nesterov, G. B. Belostotskaya,
I. V. Brailovskaya, A. V. Novozhilov, C. V. Sobol

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russian Federation;
e-mail: korotkov@SK1645.spb.edu

Received: 05 September 2019; Accepted: 29 November 2019

Thallium is known to produce one of the most complex and serious patterns of toxicity, involving a wide range of human organs and tissues. The toxic impact on biologic organisms is linked especially to the ability of Tl+ to disturb calcium homeostasis and  to permeate easily the inner mitochondrial membrane (IMM). The aim of this work was to study the effects of Tl+ on intracellular Ca2+ dynamics in rat neonatal cardiomyocytes as well as on sodium penetrability of the IMM and Tl+-induced mitochondrial permeability transition pore (MPTP) opening in isolated Ca2+-loaded rat heart mitochondria (RHM). The use of the fluorescent calcium indicator Fura 2 AM showed that Tl+ induced calcium influx across the plasmatic membrane, resulting­ in calcium ([Ca2+]i) increase in the cytoplasm. This increase was even more pronounced in experiments with accelerating of Tl+-transmembrane fluxes by nonactin. It was nevertheless abolished by the removal of extracellular Ca2+ ions, but was not inhibited by a calcium-channel blocker (nifedipine). Tl+ did not release calcium from the intracellular stores. Tl+ potentiated sodium permeability of the IMM because swelling of nonenergized RHM in medium containing TlNO3 and NaNO3 was enhanced at high Tl+ concentration. The calcium load of RHM induced MPTP opening which was accompanied by the increase of the swelling as well as the decrease of  the inner membrane potential and of state 40 (basal) and state 3UDNP (2,4-dinitrophenol-uncoupled) respiration. These effects of Tl+ were suppressed by MPTP inhibitors (cyclosporine A, ADP and n-ethylmaleimide). The data obtained showed that Tl+-stimulated influx of extracellular calcium into cardiomyocytes could cause calcium and sodium RHM overload, which lead to the MPTP opening, thus determining the sensitivity of heart muscle to thallium intoxication.

Keywords: , , , , ,

References:

  1.  Mulkey JP, Oehme FW. A review of thallium toxicity. Vet Hum Toxicol. 1993 Oct;35(5):445-53. PubMed
  2. Schoer J. Thallium. In: Hutzinger O (ed) Handbook of Environmental Chemistry. Anthropogenic Compounds. Springer, New York, 1984. p. 143-214. CrossRef
  3. Repetto G, del Peso A, Repetto M. Human thallium toxicity. Nriagu JO (ed) Thallium in the environment.  John Wiley & Sons Inc, New York, 1998. P. 167-199.
  4. Hughes MN, Man WK, Whaler BC. The toxicity of thallium(I) to cardiac and skeletal muscle. Chem Biol Interact. 1978 Oct;23(1):85-97. PubMed, CrossRef
  5. Nadel HR. Thallium-201 for oncological imaging in children. Semin Nucl Med. 1993 Jul;23(3):243-54. PubMed, CrossRef
  6. McCall D, Zimmer LJ, Katz AM. Effect of ischemia-related metabolic factors on thallium exchange in cultured rat myocardial cells. Can J Cardiol. 1986 May-Jun;2(3):176-83. PubMed
  7. Fukumoto M, Kurohara A, Yoshimura N, Yoshida D, Akagi N, Yoshida S. Relationship between ATP synthesis and 201Tl uptake in transformed and non-transformed cell lines. Nucl Med Commun. 1998 Dec;19(12):1169-75. PubMed, CrossRef
  8. Herman MM, Bensch KG. Light and electron microscopic studies of acute and chronic thallium intoxication in rats. Toxicol Appl Pharmacol. 1967 Mar;10(2):199-222. PubMed, CrossRef
  9. Woods JS, Fowler BA. Alteration of hepatocellular structure and function by thallium chloride: ultrastructural, morphometric, and biochemical studies. Toxicol Appl Pharmacol. 1986 Apr;83(2):218-29. PubMed, CrossRef
  10. Kiliç GA, Kutlu M. Effects of exogenous metallothionein against thallium-induced oxidative stress in rat liver. Food Chem Toxicol. 2010 Mar;48(3):980-7. PubMed, CrossRef
  11. Fukumoto M, Yoshida D, Yoshida S. Subcellular distribution of thallium: morphological and quantitative study in rat myocardium. Ann Nucl Med. 1997 Nov;11(4):291-7. PubMed, CrossRef
  12. Saris NE, Skulskii IA, Savina MV, Glasunov VV. Mechanism of mitochondrial transport of thallous ions. J Bioenerg Biomembr. 1981 Apr;13(1-2):51-9. PubMed, CrossRef
  13. Ichas F, Mazat JP. From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low- to high-conductance state. Biochim Biophys Acta. 1998 Aug 10;1366(1-2):33-50. PubMed, CrossRef
  14. Zierold K. Heavy metal cytotoxicity studied by electron probe X-ray microanalysis of cultured rat hepatocytes. Toxicol In Vitro. 2000 Dec;14(6):557-63.
    PubMed, CrossRef
  15. Korotkov SM, Saris NE. Influence of Tl(+) on mitochondrial permeability transition pore in Ca(2+)-loaded rat liver mitochondria. J Bioenerg Biomembr. 2011 Apr;43(2):149-62. PubMed, CrossRef
  16. Korotkov SM, Nesterov VP, Brailovskaya IV, Furaev VV, Novozhilov AV. Tl(+) induces both cationic and transition pore permeability in the inner membrane of rat heart mitochondria. J Bioenerg Biomembr. 2013 Dec;45(6):531-9. PubMed, CrossRef
  17. Sobol CV, Korotkov SM, Belostotskaya GB, Nesterov VP. The influence of probiotics and probiotic product on respiration of mitochondria and intracellular calcium signal in cells of cardiovascular system. Biochemistry (Mosc). Suppl Series A: Membr Cell Biol. 2013;7(4):294-301.  CrossRef
  18. Panov A, Kubalik N, Zinchenko N, Hemendinger R, Dikalov S, Bonkovsky HL. Respiration and ROS production in brain and spinal cord mitochondria of transgenic rats with mutant G93a Cu/Zn-superoxide dismutase gene. Neurobiol Dis. 2011 Oct;44(1):53-62.  PubMed, CrossRef
  19. Waldmeier PC, Feldtrauer JJ, Qian T, Lemasters JJ. Inhibition of the mitochondrial permeability transition by the nonimmunosuppressive cyclosporin derivative NIM811. Mol Pharmacol. 2002 Jul;62(1):22-9. PubMed, CrossRef
  20. Korotkov SM, Glazunov VV, Yagodina OV. Increase in the toxic effects of Tl+ on isolated rat liver mitochondria in the presence of nonactin. J Biochem Mol Toxicol. 2007;21(2):81-91. PubMed, CrossRef
  21. Korotkov SM, Konovalova SA, Brailovskaya IV, Saris NE. To involvement the conformation of the adenine nucleotide translocase in opening the Tl(+)-induced permeability transition pore in Ca(2+)-loaded rat liver mitochondria. Toxicol In Vitro. 2016 Apr;32:320-32. PubMed, CrossRef
  22. Rusznyák I, György L, Ormai S, Millner T. On some potassium-like qualities of the thalliumion. Experientia. 1968 Aug 15;24(8):809-10. PubMed, CrossRef
  23. Talbot PA. Nature of increase in quantal release by the thallous ion at frog end plates with and without nerve stimulation. J Gen Physiol. 1992 Nov;100(5):881-901. PubMed, PubMedCentral, CrossRef
  24. Skulskii IA, Savina MV, Glasunov VV, Saris NE. Electrophoretic transport of T1+ in mitochondria. J Membr Biol. 1978 Dec 15;44(2):187-94.
    PubMed, CrossRef
  25. Shier WT, DuBourdieu DJ. Sodium- and calcium-dependent steps in the mechanism of neonatal rat cardiac myocyte killing by ionophores. I. The sodium-carrying ionophore, monensin. Toxicol Appl Pharmacol. 1992 Sep;116(1):38-46. PubMed, CrossRef
  26. Brierley GP, Jurkowitz M. On the mechanism of energy-dependent contraction of swollen mitochondria. Biochem Biophys Res Commun. 1976 Jan 12;68(1):82-8. PubMed, CrossRef
  27. Perrin DD.  Stability Constants of Metal-ion Complexes. Part B. Organic Ligands. Pergamon Press, New York, 1979. 1263 p.
  28. Melnick RL, Monti LG, Motzkin SM. Uncoupling of mitochondrial oxidative phosphorylation by thallium. Biochem Biophys Res Commun. 1976 Mar 8;69(1):68-73. PubMed, CrossRef
  29. Korotkov SM. Effects of Tl(+) on ion permeability, membrane potential and respiration of isolated rat liver mitochondria. J Bioenerg Biomembr. 2009 Jun;41(3):277-87. PubMed, CrossRef
  30. Fu JD, Yu HM, Wang R, Liang J, Yang HT. Developmental regulation of intracellular calcium transients during cardiomyocyte differentiation of mouse embryonic stem cells. Acta Pharmacol Sin. 2006 Jul;27(7):901-10. PubMed, CrossRef
  31. Delano ML, Sands H, Gallagher BM. Transport of 42K+, 201Tl+ and [99mTc(dmpe)2.Cl2]+ by neonatal rat myocyte cultures. Biochem Pharmacol. 1985 Sep 15;34(18):3377-80. PubMed, CrossRef
  32. Peluffo RD, Berlin JR. Electrogenic K+ transport by the Na(+)-K+ pump in rat cardiac ventricular myocytes. J Physiol. 1997 May 15;501(Pt 1):33-40.
    PubMed, PubMedCentral, CrossRef
  33. Ojcius DM, Zychlinsky A, Zheng LM, Young JD. Ionophore-induced apoptosis: role of DNA fragmentation and calcium fluxes. Exp Cell Res. 1991 Nov;197(1):43-9. PubMed, CrossRef
  34. Fox J, Ciani S. Experimental and theoretical studies on Tl+ interactions with the cation-selective channel of the sarcoplasmic reticulum. J Membr Biol. 1985;84(1):9-23. PubMed, CrossRef
  35. Korotkov SM, Brailovskaya IV, Kormilitsyn BN, Furaev VV. Tl(+) showed negligible interaction with inner membrane sulfhydryl groups of rat liver mitochondria, but formed complexes with matrix proteins. J Biochem Mol Toxicol. 2014 Apr;28(4):149-56. PubMed, CrossRef
  36. Weaver CD, Harden D, Dworetzky SI, Robertson B, Knox RJ. A thallium-sensitive, fluorescence-based assay for detecting and characterizing potassium channel modulators in mammalian cells. J Biomol Screen. 2004 Dec;9(8):671-7. PubMed, CrossRef
  37. Jørgensen S, Johansen TH, Dyhring T. Fluorescence-based Tl(+)-influx assays as a novel approach for characterization of small-conductance Ca(2+)-activated K(+) channel modulators. Methods Mol Biol. 2008;491:257-66. PubMed, CrossRef
  38. Hanzel CE, Verstraeten SV. Tl(I) and Tl(III) activate both mitochondrial and extrinsic pathways of apoptosis in rat pheochromocytoma (PC12) cells. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):59-70. PubMed, CrossRef
  39. Pourahmad J, Eskandari MR, Daraei B. A comparison of hepatocyte cytotoxic mechanisms for thallium (I) and thallium (III). Environ Toxicol. 2010 Oct;25(5):456-67. PubMed, CrossRef
  40. Wojtovich AP, Williams DM, Karcz MK, Lopes CM, Gray DA, Nehrke KW, Brookes PS. A novel mitochondrial K(ATP) channel assay. Circ Res. 2010 Apr 16;106(7):1190-6. PubMed, PubMedCentral, CrossRef
  41. Testai L, Martelli A, Marino A, D’Antongiovanni V, Ciregia F, Giusti L, Lucacchini A, Chericoni S, Breschi MC, Calderone V. The activation of mitochondrial BK potassium channels contributes to the protective effects of naringenin against myocardial ischemia/reperfusion injury. Biochem Pharmacol. 2013 Jun 1;85(11):1634-43. PubMed, CrossRef
  42. Nalyvajko NV, Vovkanych LS, Dubyt’ky LO. Inhibitory analysis of the monovalent metals’ cations interaction with the system of Na+-dependent Ca2+ efflux from the liver mitochondria. Ukr Biokhim Zhurn. 2006 Sep-Oct;78(5):44-50. (In Ukrainian). PubMed
  43. Korotkov SM, Emel’yanova LV, Yagodina OV. Inorganic phosphate stimulates the toxic effects of Tl+ in rat liver mitochondria. J Biochem Mol Toxicol. 2008 May-Jun;22(3):148-57. PubMed, CrossRef
  44. Varanyuwatana P, Halestrap AP. The roles of phosphate and the phosphate carrier in the mitochondrial permeability transition pore. Mitochondrion. 2012 Jan;12(1):120-5. PubMed, PubMedCentral, CrossRef
  45. Korotkov SM, Konovalova SA, Nesterov VP, Brailovskaya IV. Mersalyl prevents the Tl+-induced permeability transition pore opening in the inner membrane of Ca2+-loaded rat liver mitochondria. Biochem Biophys Res Commun. 2018 Jan 8;495(2):1716-1721. PubMed, CrossRef
  46. Korotkov SM, Brailovskaya IV, Shumakov AR, Emelyanova LV. Closure of mitochondrial potassium channels favors opening of the Tl(+)-induced permeability transition pore in Ca(2+)-loaded rat liver mitochondria. J Bioenerg Biomembr. 2015 Jun;47(3):243-54. PubMed, CrossRef
  47. Korotkov S, Konovalova S, Emelyanova L, Brailovskaya I. Y3+, La3+, and some bivalent metals inhibited the opening of the Tl+-induced permeability transition pore in Ca2+-loaded rat liver mitochondria. J Inorg Biochem. 2014 Dec;141:1-9.  PubMed, CrossRef
  48. Halestrap AP, Brenner C. The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. Curr Med Chem. 2003 Aug;10(16):1507-25. PubMed, CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.