title: Involvement of palmitate/Ca2+(Sr2+)-induced pore in the cycling of ions across the mitochondrial membrane.
abstract: The palmitate/Ca2+-induced (Pal/Ca2+) pore, which is formed due to the unique feature of long-chain saturated fatty acids to bind Ca2+ with high affinity, has been shown to play an important role in the physiology of mitochondria. The present study demonstrates that the efflux of Ca2+ from rat liver mitochondria induced by ruthenium red, an inhibitor of the energy-dependent Ca2+ influx, seems to be partly due to the opening of Pal/Ca2+ pores. Exogenous Pal stimulates the efflux. Measurements of pH showed that the Ca2+-induced alkalization of the mitochondrial matrix increased in the presence of Pal. The influx of Ca2+ (Sr2+) also induced an outflow of K+ followed by the reuptake of the ion by mitochondria. The outflow was not affected by a K+/H+ exchange blocker, and the reuptake was prevented by an ATP-dependent K+ channel inhibitor. It was also shown that the addition of Sr2+ to mitochondria under hypotonic conditions was accompanied by reversible cyclic changes in the membrane potential, the concentrations of Sr2+ and K+ and the respiratory rate. The cyclic changes were effectively suppressed by the inhibitors of Ca2+-dependent phospholipase A2, and a new Sr2+ cycle could only be initiated after the previous cycle was finished, indicating a refractory period in the mitochondrial sensitivity to Sr2+. All of the Ca2+- and Sr2+-induced effects were observed in the presence of cyclosporin A. This paper discusses a possible role of Pal/Ca2+ pores in the maintenance of cell ion homeostasis.
authors.affiliation: Institute of Theoretical and Experimental Biophysics RAS, 142290 Pushchino, Moscow Region, Russia. Electronic address: mironova40@mail.ru.
authors.forename: Galina D
authors.initials: GD
authors.lastname: Mironova
authors.affiliation: University of Helsinki, Helsinki, POB 56 Biocenter 1, FIN-00014 Finland.
authors.forename: Nils-Erik L
authors.initials: NE
authors.lastname: Saris
authors.affiliation: Institute of Theoretical and Experimental Biophysics RAS, 142290 Pushchino, Moscow Region, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Belosludtseva
authors.affiliation: Institute of Theoretical and Experimental Biophysics RAS, 142290 Pushchino, Moscow Region, Russia.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Agafonov
authors.affiliation: Al-Farabi Kazakh National University, 050040 Almaty, Kazakhstan.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Elantsev
authors.affiliation: Institute of Theoretical and Experimental Biophysics RAS, 142290 Pushchino, Moscow Region, Russia.
authors.forename: Konstantin N
authors.initials: KN
authors.lastname: Belosludtsev
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent; D016572:Cyclosporine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D019308:Palmitic Acid / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D027961:Potassium-Hydrogen Antiporters / Q000378:metabolism; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology; D013324:Strontium / Q000378:metabolism*
chemical_list: D002413:Cations, Divalent; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D026902:Potassium Channel Blockers; D027961:Potassium-Hydrogen Antiporters; D012430:Ruthenium Red; D019308:Palmitic Acid; D016572:Cyclosporine; D011188:Potassium; D002118:Calcium; D013324:Strontium
keywords: Ca(2+) cycle; Calcium; Lipid pore; Mitochondria; Palmitic acid; Strontium