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Previously we have shown that opening of the mitochondrial permeability transition pore in its low conductance state is the case in hepatocytes of the Baltic lamprey (Lampetra fluviatilis L.) during reversible metabolic depression taking place in the period of its prespawning migration when the exogenous feeding is switched off. The depression is observed in the last year of the lamprey life cycle and is conditioned by reversible mitochondrial dysfunction (mitochondrial uncoupling in winter and coupling in spring). To further elucidate the mechanism(s) of induction of the mitochondrial permeability transition pore in the lamprey liver, we used Cd2+ and Ca2+ plus Pi as the pore inducers. We found that Ca2+ plus Pi induced the high-amplitude swelling of the isolated "winter" mitochondria both in isotonic sucrose and ammonium nitrate medium while both low and high Cd2+ did not produce the mitochondrial swelling in these media. Low Cd2+ enhanced the inhibition of basal respiration rate of the "winter" mitochondria energized by NAD-dependent substrates whereas the same concentrations of the heavy metal evoked its partial stimulation on FAD-dependent substrates. The above changes produced by Cd2+ or Ca2+ plus Pi in the "winter" mitochondria were only weakly (if so) sensitive to cyclosporine A (a potent pharmacological desensitizer of the nonselective pore) added alone and they were not sensitive to dithiothreitol (a dithiol reducing agent). Under monitoring of the transmembrane potential of the "spring" lamprey liver mitochondria, we revealed that Cd2+ produced its decrease on both types of the respiratory substrates used that was strongly hampered by cyclosporine A, and the membrane potential was partially restored by dithiothreitol. The effects of different membrane permeability modulators on the lamprey liver mitochondria function and the seasonal changes in their action are discussed. [ABSTRACT FROM AUTHOR]

Nonrespiring rat-liver mitochondria swell in media containing high concentrations of thallous nitrate, indicating passive penetration of TI+ This swelling could be further stimulated by 10 nM or more nonactin while even 1μM valinomycin was without effect. Nonactin was also much more potent than valinomycin in stimulating swelling of respiring mitochondria in the presence of thallous acetate. It is evident that nonactin acts as a potent lonophore of TI + able to promote both the passive and energized uptake of TI + in mitochondria. The distribution of TI+, present in trace concentrations below 1 mM, was measured during energisation by respiration both in the presence and absence of ionophores. Respiration induced net uptake of TI+ only in the presence of lonophores, though TI + as a permeant cation was expected to sense respiration-induced changes in the membrane potential. The data may be interpreted as indicating that no transmembrane potential is formed upon energisatiom, but localized fields, which are able to interact with the lipophilic ionophore complexes of TI +, but not with the hydrophilic cation Tl+ This interpretation is valid only if thermodynamic equilibrium has been reached. [ABSTRACT FROM AUTHOR]