Journal of Bioenergetics and Biomembranes

, Volume 45, Issue 6, pp 531–539 | Cite as

Tl+ induces both cationic and transition pore permeability in the inner membrane of rat heart mitochondria

  • Sergey M. Korotkov
  • Vladimir P. Nesterov
  • Irina V. Brailovskaya
  • Viktor V. Furaev
  • Artemy V. Novozhilov


Effects of Tl+ were studied in experiments with isolated rat heart mitochondria (RHM) injected into 400 mOsm medium containing TlNO3 and a nitrate salt (KNO3 or NH4NO3) or TlNO3 and sucrose. Tl+ increased permeability of the inner membrane of the RHM to K+ and H+. This manifested as an increase of the non-energized RHM swelling, in the order of sucrose < K+ < NH4 +, respectively. After succinate administration, the swollen RHM contracted. The Tl+-induced opening of the mitochondrial permeability pore (MPTP) in Ca2+-loaded rat heart mitochondria increased both the swelling and the inner membrane potential dissipation, as well as decreased basal state and 2,4-dinitrophenol-stimulated respiration. These effects of Tl+ were suppressed by the MPTP inhibitors (cyclosporine A, ADP, bongkrekic acid, and n-ethylmaleimide), activated in the presence of the MPTP inducer (carboxyatractyloside) or mitoKATP inhibitor (5-hydroxydecanoate), but were not altered in the presence of mitoKATP agonists (diazoxide or pinacidil). We suggest that the greater sensitivity of heart and striated muscles, versus liver, to thallium salts in vivo can result in more vigorous Tl+ effects on muscle cell mitochondria.


Tl+ Ca2+ Mitochondrial permeability transition Mitochondrial bioenergetics Mitochondrial swelling Rat heart mitochondria 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arbab AS, Koizumi K, Toyama K, Arai T, Araki T (1998) Technetium-99m-tetrofosmin, technetium-99m-MIBI and thallium-201 uptake in rat myocardial cells. J Nucl Med 39(2):266–271Google Scholar
  2. Baines CP (2009) The molecular composition of the mitochondrial permeability transition pore. J Mol Cell Cardiol 46(6):850–857CrossRefGoogle Scholar
  3. Barroso-Moguel R, Mendez-Armenta M, Villeda-Hernandez J, Rios C, Galvan-Arzate S (1996) Experimental neuromyopathy induced by thallium in rats. J Appl Toxicol 16(5):385–389CrossRefGoogle Scholar
  4. Bernardi P (1999) Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol Rev 79(4):1127–1155Google Scholar
  5. Brierley GP, Jung DW (1988) K+/H+ antiport in mitochondria. J Bioenerg Biomembr 20(2):193–209CrossRefGoogle Scholar
  6. Brierley GP, Jurkowitz M, Scott KM, Merola AJ (1970) Ion transport by heart mitochondria. XX. Factors affecting passive osmotic swelling of isolated mitochondria. J Biol Chem 245(20):5404–5411Google Scholar
  7. Brierley GP, Jurkowitz M, Chávez E, Jung DW (1977) Energy-dependent contraction of swollen heart mitochondria. J Biol Chem 252(22):7932–7939Google Scholar
  8. Brierley GP, Davis MH, Jung DW (1988) Respiration-dependent contraction of swollen heart mitochondria: participation of the K+/H+ antiporter. J Bioenerg Biomembr 20(2):229–242CrossRefGoogle Scholar
  9. Cheng Y, Debska-Vielhaber G, Siemen D (2010) Interaction of mitochondrial potassium channels with the permeability transition pore. FEBS Lett 584(10):2005–2012CrossRefGoogle Scholar
  10. Costa AD, Jakob R, Costa CL, Andrukhiv K, West IC, Garlid KD (2006) The mechanism by which the mitochondrial ATP-sensitive K+ channel opening and H2O2 inhibit the mitochondrial permeability transition. J Biol Chem 281(30):20801–20808CrossRefGoogle Scholar
  11. Crestanello JA, Doliba NM, Babsky AM, Doliba NM, Niibori K, Osbakken MD, Whitman GJ (2000) Opening of potassium channels protects mitochondrial function from calcium overload. J Surg Res 94(2):116–123CrossRefGoogle Scholar
  12. Delano ML, Sands H, Gallagher BM (1985) Transport of 42K+, 201Tl+ and [99mTc(dmpe)2 · Cl2]+ by neonatal rat myocyte cultures. Biochem Pharmacol 34(18):3377–3380CrossRefGoogle Scholar
  13. Deshimaru M, Miyakawa T, Sumiyoshi S, Yasuoka F, Kawano K (1977) Electron microscopic study of experimental thallotoxicosis. Folia Psychiatr Neurol Jpn 31(2):269–275Google Scholar
  14. Douglas KT, Bunni MA, Baindur SR (1990) Thallium in biochemistry. Int J Biochem 22(5):429–438CrossRefGoogle Scholar
  15. Edelmann L (1988) The cell water problem posed by electron microscopic studies of ion binding in muscle. Scanning Microsc 2(2):851–856Google Scholar
  16. Foster DB, Ho AS, Rucker J, Garlid AO, Chen L, Sidor A, Garlid KD, O’Rourke B (2012) Mitochondrial ROMK channel is a molecular component of mitoKATP. Circ Res 111(4):446–454CrossRefGoogle Scholar
  17. Fox J, Ciani S (1985) Experimental and theoretical studies on Tl+ interactions with the cation-selective channel of the sarcoplasmic reticulum. J Membr Biol 84(1):9–23CrossRefGoogle Scholar
  18. Fukumoto M, Yoshida D, Yoshida S (1997) Subcellular distribution of thallium: morphological and quantitative study in rat myocardium. Ann Nucl Med 11(4):291–297CrossRefGoogle Scholar
  19. Goel A, Aggarwal P (2007) Pesticide poisoning. Natl Med J India 20(4):182–191Google Scholar
  20. Halestrap AP (2009) What is the mitochondrial permeability transition pore? J Mol Cell Cardiol 46(6):821–831CrossRefGoogle Scholar
  21. Halestrap AP, Brenner C (2003) The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. Curr Med Chem 10(16):1507–1525CrossRefGoogle Scholar
  22. Hanzel CE, Verstraeten SV (2006) Thallium induces hydrogen peroxide generation by impairing mitochondrial function. Toxicol Appl Pharmacol 216(3):485–492CrossRefGoogle Scholar
  23. Hanzel CE, Verstraeten SV (2009) Tl(I) and Tl(III) activate both mitochondrial and extrinsic pathways of apoptosis in rat pheochromocytoma (PC12) cells. Toxicol Appl Pharmacol 236(1):59–70CrossRefGoogle Scholar
  24. Hsieh PJ, Su HY, Lo HS, Chen ML (2012) Dipyridamole 201Tl myocardial SPECT in the assessment of a patient with myocardial bridging and concomitant atherosclerotic coronary artery disease. Clin Nucl Med 37(10):e257–e262CrossRefGoogle Scholar
  25. Hughes MN, Man WK, Whaler BC (1978) The toxicity of thallium(I) to cardiac and skeletal muscle. Chem Biol Interact 23(1):85–97CrossRefGoogle Scholar
  26. Hunter DR, Haworth RA, Goknur AB, Hegge JO, Berkoff HA (1986) Control of thallium and sodium fluxes in isolated adult rat heart cells by anthopleurin-A, verapamil and magnesium. J Mol Cell Cardiol 18(11):1125–1132CrossRefGoogle Scholar
  27. Ichas F, Mazat JP (1998) From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low- to high-conductance state. Biochim Biophys Acta 1366(1–2):33–50Google Scholar
  28. Korotkov SM (2009) Effects of Tl+ on ion permeability, membrane potential and respiration of isolated rat liver mitochondria. J Bioenerg Biomembr 41(3):277–287CrossRefGoogle Scholar
  29. Korotkov SM, Saris NE (2011) Influence of Tl+ on mitochondrial permeability transition pore in Ca2+-loaded rat liver mitochondria. J Bioenerg Biomembr 43(2):149–162CrossRefGoogle Scholar
  30. Korotkov SM, Glazunov VV, Yagodina OV (2007) Increase in the toxic effects of Tl+ on isolated rat liver mitochondria in the presence of nonactin. J Biochem Mol Toxicol 21(2):81–91CrossRefGoogle Scholar
  31. Korotkov SM, Emel’yanova LV, Yagodina OV (2008) Inorganic phosphate stimulates the toxic effects of Tl+ in rat liver mitochondria. J Biochem Mol Toxicol 22(3):148–157CrossRefGoogle Scholar
  32. Korotkov SM, Emel’yanova LV, Brailovskaya IV, Nesterov VP (2012) Effects of pinacidil and calcium on isolated rat heart mitochondria. Dokl Biochem Biophys 443:113–117CrossRefGoogle Scholar
  33. Lameijer W, van Zwieten PA (1977) Kinetic behavior of thallium in the rat. Accelerated elimination of thallium owing to treatment with potent diuretic agents. Arch Toxicol 37(4):265–273CrossRefGoogle Scholar
  34. Leung KM, Ooi VE (2000) Studies on thallium toxicity, its tissue distribution and histopathological effects in rats. Chemosphere 41(1–2):155–159CrossRefGoogle Scholar
  35. Ling GN (1977) Thallium and cesium in muscle cells compete for the adsorption sites normally occupied by K+. Physiol Chem Phys 9(3):217–225Google Scholar
  36. McCall D, Zimmer LJ, Katz AM (1985) Kinetics of thallium exchange in cultured ratmyocardial cells. Circ Res 56(3):370–376CrossRefGoogle Scholar
  37. Méndez-Armenta M, Nava-Ruiz C, Fernández-Valverde F, Sánchez-García A, Rios C (2011) Histochemical changes in muscle of rats exposed subchronically to low doses of heavy metals. Environ Toxicol Pharmacol 32(1):107–112CrossRefGoogle Scholar
  38. Mulkey JP, Oehme FW (1993) A review of thallium toxicity. Vet Hum Toxicol 35(5):445–453Google Scholar
  39. Pagnanelli RA, Basso DA (2010) Myocardial perfusion imaging with 201Tl. J Nucl Med Technol 38(1):1–3CrossRefGoogle Scholar
  40. Peluffo RD, Berlin JR (1997) Electrogenic K+ transport by the Na+-K+ pump in rat cardiac ventricular myocytes. J Physiol 501(Pt 1):33–40CrossRefGoogle Scholar
  41. Pourahmad J, Eskandari MR, Daraei B (2010) A comparison of hepatocyte cytotoxic mechanisms for thallium (I) and thallium (III). Environ Toxicol 25(5):456–467CrossRefGoogle Scholar
  42. Queliconi BB, Wojtovich AP, Nadtochiy SM, Kowaltowski AJ, Brookes PS (2011) Redox regulation of the mitochondrial KATP channel in cardioprotection. Biochim Biophys Acta 1813(7):1309–1315CrossRefGoogle Scholar
  43. Saris NE, Skulskii IA, Savina MV, Glasunov VV (1981) Mechanism of mitochondrial transport of thallous ions. J Bioenerg Biomembr 13(1/2):51–59CrossRefGoogle Scholar
  44. Skul’skiĭ IA (1977) Transport of monovalent thallium ions across mitochondrial membranes. Dokl Akad Nauk SSSR Russ 232(4):945–948Google Scholar
  45. Testai L, Martelli A, Marino A, D’Antongiovanni V, Ciregia F, Giusti L, Lucacchini A, Chericoni S, Breschi MC, Calderone V (2013) The activation of mitochondrial BK potassium channels contributes to the protective effects of naringenin against myocardial ischemia/reperfusion injury. Biochem Pharmacol 85(11):1634–1643CrossRefGoogle Scholar
  46. Varanyuwatana P, Halestrap AP (2012) The roles of phosphate and the phosphate carrier in the mitochondrial permeability transition pore. Mitochondrion 12(1):120–125CrossRefGoogle Scholar
  47. Villaverde MS, Hanzel CE, Verstraeten SV (2004) In vitro interactions of thallium with components of the glutathione-dependent antioxidant defence system. Free Radic Res 38(9):977–984CrossRefGoogle Scholar
  48. Waldmeier PC, Feldtrauer JJ, Qian T, Lemasters J (2002) Inhibition of the mitochondrial permeability transition by the nonimmunosuppressive cyclosporin derivative NIM811. Mol Pharmacol 62(1):22–29CrossRefGoogle Scholar
  49. Weaver CD, Harden D, Dworetzky SI, Robertson B, Knox RJ (2004) A thallium-sensitive, fluorescence-based assay for detecting and characterizing potassium channel modulators in mammalian cells. J Biomol Screen 9(8):671–677CrossRefGoogle Scholar
  50. Wojtovich AP, Williams DM, Karcz MK, Lopes CM, Gray DA, Nehrke KW, Brookes PS (2010) A novel mitochondrial KATP channel assay. Circ Res 106(7):1190–1196CrossRefGoogle Scholar
  51. Zierold K (2000) Heavy metal cytotoxicity studied by electron probe X-ray microanalysis of cultured rat hepatocytes. Toxicol in Vitro 14(6):557–563CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Sergey M. Korotkov
    • 1
  • Vladimir P. Nesterov
    • 1
  • Irina V. Brailovskaya
    • 1
  • Viktor V. Furaev
    • 1
  • Artemy V. Novozhilov
    • 1
  1. 1.Sechenov Institute of Evolutionary Physiology and Biochemistrythe Russian Academy of SciencesSt. PetersburgRussia

Personalised recommendations