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

Abstract

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 Ca 2+ 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 Ca 2+ -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 ([Ca 2+ ] 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 Ca 2+ 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 tlNo 3 and NaNo 3 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 4 0 (basal) and state 3U DNP (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. K e y w o r d s: tl + , Ca 2+ , Na + , cardiomyocytes, rat heart mitochondria, mitochondrial permeability transition pore (MPtP).

Mitochondrial Oxidative Stress Is the General Reason for Apoptosis Induced by Different-Valence Heavy Metals in Cells and Mitochondria

“…Thallium uncoupled oxidative phosphorylation in the mitochondria of mammalian cells [7,[19][20][21]. The cytoplasmic concentration of Ca 2+ and Na + increased, while that of K + fell due to the Tl + toxic influence on rat hepatocytes and cardiomyocytes [22,23]. Unlike bivalent heavy metals, Tl + does not have any noticeable effect on either mitochondrial respiratory enzymes (NADH-, succinate-, and malate-dehydrogenases) or mitochondrial thiol groups [9,10,[24][25][26].…”