title: Y3+, La3+, and some bivalent metals inhibited the opening of the Tl+-induced permeability transition pore in Ca2+-loaded rat liver mitochondria.
abstract: We showed earlier that diminution of 2,4-dinitrophenol (DNP)-stimulated respiration and increase of both mitochondrial swelling and electrochemical potential (ΔΨmito) dissipation in medium containing TlNO3 and KNO3 were caused by opening of Tl(+)-induced mitochondrial permeability transition pore (MPTP) in the inner membrane of Ca(2+)-loaded rat liver mitochondria. The MPTP opening was studied in the presence of bivalent metal ions (Sr(2+), Ba(2+), Mn(2+), Co(2+) and Ni(2+)), trivalent metal ions (Y(3+) and La(3+)), and ruthenium red. We found that these metal ions (except Ba(2+) and Co(2+)) as well as ruthenium red inhibited to the MPTP opening that manifested in preventing both diminution of the DNP-stimulated respiration and increase of the swelling and of the ΔΨmito dissipation in medium containing TlNO3, KNO3, and Ca(2+). Inhibition of the MPTP opening by Sr(2+) and Mn(2+) is suggested because of their interaction with high affinity Ca(2+) sites, facing the matrix side and participating in the MPTP opening. The inhibitory effects of metal ions (Y(3+), La(3+), and Ni(2+)), and ruthenium red are accordingly discussed in regard to competitive and noncompetitive inhibition of the mitochondrial Ca(2+)-uniporter. High concentrations (50μM) of Y(3+) and La(3+) favored of MPTP opening in the inner membrane of rat liver mitochondria in Ca(2+) free medium containing TlNO3. The latter MPTP opening was markedly eliminated by MPTP inhibitors (cyclosporine A and ADP).
authors.affiliation: Sechenov Institute of Evolutionary Physiology and Biochemistry, the Russian Academy of Sciences, Thorez pr. 44, 194223 St. Petersburg, Russian Federation. Electronic address: korotkov@SK1645.spb.edu.
authors.forename: Sergey
authors.initials: S
authors.lastname: Korotkov
authors.affiliation: Sechenov Institute of Evolutionary Physiology and Biochemistry, the Russian Academy of Sciences, Thorez pr. 44, 194223 St. Petersburg, Russian Federation.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Konovalova
authors.affiliation: Sechenov Institute of Evolutionary Physiology and Biochemistry, the Russian Academy of Sciences, Thorez pr. 44, 194223 St. Petersburg, Russian Federation.
authors.forename: Larisa
authors.initials: L
authors.lastname: Emelyanova
authors.affiliation: Sechenov Institute of Evolutionary Physiology and Biochemistry, the Russian Academy of Sciences, Thorez pr. 44, 194223 St. Petersburg, Russian Federation.
authors.forename: Irina
authors.initials: I
authors.lastname: Brailovskaya
mesh_terms: D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002412:Cations; D019069:Cell Respiration / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D007811:Lanthanum / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology; D013793:Thallium / Q000378:metabolism / Q000494:pharmacology*; D015019:Yttrium / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002412:Cations; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D012430:Ruthenium Red; D015019:Yttrium; D000244:Adenosine Diphosphate; D007811:Lanthanum; D016572:Cyclosporine; D013793:Thallium; D019297:2,4-Dinitrophenol; D002118:Calcium
keywords: Bivalent metal ions; La(3+); Mitochondrial permeability transition; Rat liver mitochondria; Tl(+); Y(3+)