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

摘要

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 Tlsup+/sup to disturb calcium homeostasis and to permeate easily the inner mitochondrial membrane (IMM). The aim of this work was to study the effects of Tlsup+/sup on intracellular Casup2+/sup dynamics in rat neonatal cardiomyocytes as well as on sodium penetrability of the IMM and Tlsup+/sup-induced mitochondrial permeability transition pore (MPTP) opening in isolated Casup2+/sup-loaded rat heart mitochondria (RHM). The use of the fluorescent calcium indicator Fura 2 AM showed that Tlsup+/sup induced calcium influx across the plasmatic membrane, resulting in calcium ([Casup2+/sup]subi/sub) increase in the cytoplasm. This increase was even more pronounced in experiments with accelerating of Tlsup+/sup-transmembrane fluxes by nonactin. It was nevertheless abolished by the removal of extracellular Casup2+/sup ions, but was not inhibited by a calcium-channel blocker (nifedipine). Tlsup+/sup did not release calcium from the intracellular stores. Tlsup+/sup potentiated sodium permeability of the IMM because swelling of nonenergized RHM in medium containing TlNOsub3/sub and NaNOsub3/sub was enhanced at high Tlsup+/sup 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 4sub0/sub (basal) and state 3UsubDNP/sub (2,4-dinitrophenol-uncoupled) respiration. These effects of Tlsup+/sup were suppressed by MPTP inhibitors (cyclosporine A, ADP and n-ethylmaleimide). The data obtained showed that Tlsup+/sup-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.