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


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

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;

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: , , , , ,


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