Electrophoretic transport of Tl+ in mitochondria

Abstract

The distribution of T1+ between rat liver mitochondria and the medium was studied; millimolar or smaller concentrations of T1+ were labeled with 204T1. The T1+ distribution responded to transient diffusion potentials in a way that indicated electrophoretic movements of T1+. The diffusion potentials were induced by efflux of K+ in response to addition of valinomycin to nonrespiring mitochondria suspended in a medium with low concentrations of K+ or by efflux of H+ induced by making the medium more alkaline in the presence of a protonophorous (proton-conducting) uncoupling agent. Changes in membrane potential induced by valinomycin were followed with the aid of safranine. T1+ brought about collapse of the diffusion potential. It is concluded that T1+ is able to penetrate the mitochondrial membrane electrophoretically.

Increase in the toxic effects of Tl+ on isolated rat liver mitochondria in the presence of nonactin

“…Swelling of potassium-energized mitochondria in the 5-50 mM Tl acetate medium was markedly accelerated in the presence of nonactin ( Figure 2B). Taking into account these data, our findings argue in favor of nonactin facilitating electrophoretic transport of Tl + in energized mitochondria [3,9] (Figures 4B and 5). It was found that energized Na-loaded mitochondria swollen in 25 mM Tl acetate showed fast contraction, followed by deenergization [4].…”

“…Such a transport system can be the unregulated K + uniporter [3,6] or the K ATP channel of mitochondria [1,41] that are parts of the common transport mechanism for K + ions per se. Indeed, it was demonstrated earlier that these two parts, the nonregulated [3,4,7,9] and the regulated one [41], can be involved in energy-linked transport of Tl + in mitochondria. Another reason for the decrease may be amplification of the uncoupling effect of Tl + on the State 4 mitochondrial respiration in the presence of nonactin ( Figure 3A).…”

“…For example, micromolar thallium concentrations are applied in isotope [4,9,10,12] ( Figures 4 and 5) and fluorescent [9,21] techniques with isolated mitochondria and cells. On the other hand, millimolar thallium concentrations are commonly used in studies on swelling [3,7,9,16] (Figures 1 and 2), respiration [7,17] (Figure 3), potassium ion flux [8,16], protein fractioning [34] of isolated mitochondria, or potassium channels of frog oocytes [46,47]. It has been long believed by analogy with the effect of heavy metals such as Cd 2+ , Hg 2+ , and Pb 2+ [40,48,49] and cadmium(II) organic complexes [33] that toxic influence of thallium salts on cells and mitochondria is due to the reaction of Tl + with SH groups of cellular and mitochondrial enzymes and to possible Tl + inhibition of respiratory enzymes of mitochondria [13,15].…”

“…• C by the milliporic filtration procedure [29] described in detail by Skulskii et al [9,30]. Mitochondria (1 mg/mL of protein) were incubated in the medium containing 200 mM sucrose and 5 mM succinate (Figures 4 and 5), 1 µM rotenone, and 1 µg/mL of oligomycin.…”

Inorganic phosphate stimulates the toxic effects of Tl+ in rat liver mitochondria

“…At the same time, no marked effect of Tl + on state 3 and 2,4-dinitrophenol(DNP)-stimulated respiration [2][3][4]6] and on mitochondrial respiratory enzymes [3,[8][9][10] was found. Considering that the inner mitochondrial membrane is easily permeable to Tl + [3,11], nonenergized mitochondria can markedly swell in TlNO 3 medium [6,7,12]. Subsequent energization of the mitochondria stimulated their contraction through the Tl + /H + exchange mechanism [6,7].…”