title: Calcium-induced contraction of sarcomeres changes the regulation of mitochondrial respiration in permeabilized cardiac cells.
abstract: The relationships between cardiac cell structure and the regulation of mitochondrial respiration were studied by applying fluorescent confocal microscopy and analysing the kinetics of mitochondrial ADP-stimulated respiration, during calcium-induced contraction in permeabilized cardiomyocytes and myocardial fibers, and in their 'ghost' preparations (after selective myosin extraction). Up to 3 microm free calcium, in the presence of ATP, induced strong contraction of permeabilized cardiomyocytes with intact sarcomeres, accompanied by alterations in mitochondrial arrangement and a significant decrease in the apparent K(m) for exogenous ADP and ATP in the kinetics of mitochondrial respiration. The V(max) of respiration showed a moderate (50%) increase, with an optimum at 0.4 microm free calcium and a decrease at higher calcium concentrations. At high free-calcium concentrations, the direct flux of ADP from ATPases to mitochondria was diminished compared to that at low calcium levels. All of these effects were unrelated either to mitochondrial calcium overload or to mitochondrial permeability transition and were not observed in 'ghost' preparations after the selective extraction of myosin. Our results suggest that the structural changes transmitted from contractile apparatus to mitochondria modify localized restrictions of the diffusion of adenine nucleotides and thus may actively participate in the regulation of mitochondrial function, in addition to the metabolic signalling via the creatine kinase system.
authors.affiliation: Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia.
authors.forename: Tiia
authors.initials: T
authors.lastname: Anmann
authors.forename: Margus
authors.initials: M
authors.lastname: Eimre
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kuznetsov
authors.forename: Tatiana
authors.initials: T
authors.lastname: Andrienko
authors.forename: Tuuli
authors.initials: T
authors.lastname: Kaambre
authors.forename: Peeter
authors.initials: P
authors.lastname: Sikk
authors.forename: Evelin
authors.initials: E
authors.lastname: Seppet
authors.forename: Toomas
authors.initials: T
authors.lastname: Tiivel
authors.forename: Marko
authors.initials: M
authors.lastname: Vendelin
authors.forename: Enn
authors.initials: E
authors.lastname: Seppet
authors.forename: Valdur A
authors.initials: VA
authors.lastname: Saks
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000502:physiology; D019069:Cell Respiration / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000378:metabolism*
chemical_list: D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002118:Calcium