Effects of Tl(+) on ion permeability, membrane potential and respiration of isolated rat liver mitochondria.
It is known that permeability of the inner mitochondrial membrane is low to most univalent cations (K(+), Na(+), H(+)) but high to Tl(+). Swelling, state 4, state 3, and 2,4-dinitrophenol (DNP)-stimulated respiration as well as the membrane potential (DeltaPsi(mito)) of rat liver mitochondria were studied in media containing 0-75 mM TlNO(3) either with 250 mM sucrose or with 125 mM nitrate salts of other monovalent cations (KNO(3), or NaNO(3), or NH(4)NO(3)). Tl(+) increased permeability of the inner mitochondrial membrane to K(+), Na(+), and H(+), that was manifested as stimulation of the swelling of nonenergized and energized mitochondria as well as via an increase of state 4 and dissipation of DeltaPsi(mito). These effects of Tl(+) increased in the order of sucrose <K(+) <Na(+) <or= NH(4)(+). They were stimulated by inorganic phosphate and decreased by ADP, Mg(2+), and cyclosporine A. Contraction of energized mitochondria, swollen in the nitrate media, was markedly inhibited by quinine. It suggests participation of the mitochondrial K(+)/H(+) exchanger in extruding of Tl(+)-induced excess of univalent cations from the mitochondrial matrix. It is discussed that Tl(+) (like Cd(2+) and other heavy metals) increases the ion permeability of the inner membrane of mitochondria regardless of their energization and stimulates the mitochondrial permeability transition pore in low conductance state. The observed decrease of state 3 and DNP-stimulated respiration in the nitrate media resulted from the mitochondrial swelling rather than from an inhibition of respiratory enzymes as is the case with the bivalent heavy metals.
Korotkov
Sergey M
SM
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia. korotkov@SK1645.spb.edu
D000818:Animals; D019069:Cell Respiration / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology; D010539:Permeability / Q000187:drug effects; D051381:Rats; D013053:Spectrophotometry; D013793:Thallium / Q000494:pharmacology*
D013793:Thallium; C042172:thallium nitrate