Influence of Tl(+) on the Ca(2+) and Na(+) movement across rat neonatal cardiomyocytes and rat heart mitochondria membranes
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...
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| Format: | Article |
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National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry
2020-02-01
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| Series: | The Ukrainian Biochemical Journal |
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| Online Access: | http://ukrbiochemjournal.org/wp-content/uploads/2020/02/Korotkov_1_20.pdf |
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| author | S. M. Korotkov V. P. Nesterov G. B. Belostotskaya I. V. Brailovskaya A. V. Novozhilov C. V. Sobol |
| author_facet | S. M. Korotkov V. P. Nesterov G. B. Belostotskaya I. V. Brailovskaya A. V. Novozhilov C. V. Sobol |
| author_sort | S. M. Korotkov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T13:51:03Z |
| format | Article |
| id | doaj.art-3d549e6457f54629b04ca6440d6b9146 |
| institution | Directory Open Access Journal |
| issn | 2409-4943 2413-5003 |
| language | English |
| last_indexed | 2024-03-11T13:51:03Z |
| publishDate | 2020-02-01 |
| publisher | National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry |
| record_format | Article |
| series | The Ukrainian Biochemical Journal |
| spelling | doaj.art-3d549e6457f54629b04ca6440d6b91462023-11-02T09:03:57ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryThe Ukrainian Biochemical Journal2409-49432413-50032020-02-01921415510.15407/ubj92.01.041Influence of Tl(+) on the Ca(2+) and Na(+) movement across rat neonatal cardiomyocytes and rat heart mitochondria membranesS. M. Korotkov0V. P. Nesterov1G. B. Belostotskaya2I. V. Brailovskaya3A. V. Novozhilov4C. V. Sobol5Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russian FederationSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russian FederationSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russian FederationSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russian FederationSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russian FederationSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russian FederationThallium 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.http://ukrbiochemjournal.org/wp-content/uploads/2020/02/Korotkov_1_20.pdfca(2+)cardiomyocytesmitochondrial permeability transition pore (mptp)na(+)rat heart mitochondriatl(+) |
| spellingShingle | S. M. Korotkov V. P. Nesterov G. B. Belostotskaya I. V. Brailovskaya A. V. Novozhilov C. V. Sobol Influence of Tl(+) on the Ca(2+) and Na(+) movement across rat neonatal cardiomyocytes and rat heart mitochondria membranes The Ukrainian Biochemical Journal ca(2+) cardiomyocytes mitochondrial permeability transition pore (mptp) na(+) rat heart mitochondria tl(+) |
| title | Influence of Tl(+) on the Ca(2+) and Na(+) movement across rat neonatal cardiomyocytes and rat heart mitochondria membranes |
| title_full | Influence of Tl(+) on the Ca(2+) and Na(+) movement across rat neonatal cardiomyocytes and rat heart mitochondria membranes |
| title_fullStr | Influence of Tl(+) on the Ca(2+) and Na(+) movement across rat neonatal cardiomyocytes and rat heart mitochondria membranes |
| title_full_unstemmed | Influence of Tl(+) on the Ca(2+) and Na(+) movement across rat neonatal cardiomyocytes and rat heart mitochondria membranes |
| title_short | Influence of Tl(+) on the Ca(2+) and Na(+) movement across rat neonatal cardiomyocytes and rat heart mitochondria membranes |
| title_sort | influence of tl on the ca 2 and na movement across rat neonatal cardiomyocytes and rat heart mitochondria membranes |
| topic | ca(2+) cardiomyocytes mitochondrial permeability transition pore (mptp) na(+) rat heart mitochondria tl(+) |
| url | http://ukrbiochemjournal.org/wp-content/uploads/2020/02/Korotkov_1_20.pdf |
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