Tl(+) induces both cationic and transition pore permeability in the inner membrane of rat heart mitochondria.
Effects of Tl(+) were studied in experiments with isolated rat heart mitochondria (RHM) injected into 400 mOsm medium containing TlNO3 and a nitrate salt (KNO3 or NH4NO3) or TlNO3 and sucrose. Tl(+) increased permeability of the inner membrane of the RHM to K(+) and H(+). This manifested as an increase of the non-energized RHM swelling, in the order of sucrose < K(+) < NH4 (+), respectively. After succinate administration, the swollen RHM contracted. The Tl(+)-induced opening of the mitochondrial permeability pore (MPTP) in Ca(2+)-loaded rat heart mitochondria increased both the swelling and the inner membrane potential dissipation, as well as decreased basal state and 2,4-dinitrophenol-stimulated respiration. These effects of Tl(+) were suppressed by the MPTP inhibitors (cyclosporine A, ADP, bongkrekic acid, and n-ethylmaleimide), activated in the presence of the MPTP inducer (carboxyatractyloside) or mitoKATP inhibitor (5-hydroxydecanoate), but were not altered in the presence of mitoKATP agonists (diazoxide or pinacidil). We suggest that the greater sensitivity of heart and striated muscles, versus liver, to thallium salts in vivo can result in more vigorous Tl(+) effects on muscle cell mitochondria.
Sechenov Institute of Evolutionary Physiology and Biochemistry, the Russian Academy of Sciences, Thorez pr. 44, 194223, St. Petersburg, Russia, korotkov@SK1645.spb.edu.
Sergey M
SM
Korotkov
Vladimir P
VP
Nesterov
Irina V
IV
Brailovskaya
Viktor V
VV
Furaev
Artemy V
AV
Novozhilov
D000818:Animals; D002414:Cations, Monovalent / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D019069:Cell Respiration; D004195:Disease Models, Animal; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar; D013793:Thallium / Q000494:pharmacology*
D002414:Cations, Monovalent; D013793:Thallium