Intracellular diffusion of adenosine phosphates is locally restricted in cardiac muscle
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Recent studies have revealed the structural and functional interactions between mitochondria, myofibrils and sarcoplasmic reticulum in cardiac cells. Direct channeling of adenosine phosphates between organelles identified in the experiments indicates that diffusion of adenosine phosphates is limited in cardiac cells due to very specific intracellular structural organization. However, the mode of diffusion restrictions and nature of the intracellular structures in creating the diffusion barriers is still unclear, and, therefore, a subject of active research. The aim of this work is to analyze the possible role of two principally different modes of restriction distribution for adenosine phosphates (a) the uniform diffusion restriction and (b) the localized diffusion limitation in the vicinity of mitochondria, by fitting the experimental data with the mathematical model. The reaction-diffusion model of compartmentalized energy transfer was used to analyze the data obtained from the experiments with the skinned muscle fibers, which described the following processes: mitochondrial respiration rate dependency on exogenous ADP and ATP concentrations; inhibition of endogenous ADP-stimulated respiration by pyruvate kinase (PK) and phosphoenolpyruvate (PEP) system; kinetics of oxygen consumption stabilization after addition of 2 mM MgATP or MgADP; ATPase activity with inhibited mitochondrial respiration; and buildup of MgADP concentration in the medium after addition of MgATP. The analysis revealed that only the second mechanism considered – localization of diffusion restrictions – is able to account for the experimental data. In the case of uniform diffusion restrictions, the model solution was in agreement only with two measurements: the respiration rate as a function of ADP or ATP concentrations and inhibition of respiration by PK + PEP. It was concluded that intracellular diffusion restrictions for adenosine phosphates are not distributed uniformly, but rather are localized in certain compartments of the cardiac cells.
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- 10.Saks VA, Vasil'eva E, O Y, Belikova, Kuznetsov AV, Lyapina S, Petrova L, Perov NA: Retarded diffusion of ADP in cardiomyocytes: Possible role of mitochondrial outer membrane and creatine kinase in cellular regulation of oxidative phosphorylation. Biochim Biophys Acta 1144: 134–148, 1993PubMedGoogle Scholar
- 11.Kay L, Li Z, Mericskay M, Olivares J, Tranqui L, Fontaine E, Tiivel T, Sikk P, Kaambre T, Samuel JL, Rappaport L, Usson Y, Leverve X, Paulin D, Saks VS: Study of regulation of mitochondrial respiration in vivo. An analysis of influence of ADP diffusion and possible role of cytoskeleton. Biochim Biophys Acta 1322: 41–59, 1997PubMedGoogle Scholar
- 16.Saks VA, Belikova Y, Vasilyeva E, Kuznetsov A, Fontaine E, Keriel C, Leverve X: Correlation between degree of rupture of outer mitochondrial membrane and changes of kinetics of regulation of respiration by ADP in permeabilized heart and liver cells. Biochem Biophys Res Commun 208: 919–926, 1995CrossRefPubMedGoogle Scholar
- 19.Abraham MR, Selivanov VA, Hodgson DM, Pucar D, Zingman LV, Wieringa B, Dzeja PP, Alekseev AE, Terzic A: Coupling of cell energetics with membrane metabolic sensing. Integrative signaling through creatine kinase phosphotransfer disrupted by M-CK gene knock-out. J Biol Chem 277: 24427–24434, 2002CrossRefPubMedGoogle Scholar
- 20.Selivanov VA, Alekseev AE, Hodgson DM, Dzeja PP, Terzic A: Nucleotide-gated KATP channels integrated with creatine and adenylate kinases: Amplification, tuning and sensing of energetic signals in the compartmentalized cellular environment. Mol Cell Biochem 256/257: 243–256, 2004CrossRefGoogle Scholar
- 21.Nicholls DG, Ferguson SJ: In: Bioenergetics 3. Academic Press, 2002Google Scholar
- 22.Bruaset AM, Langtagen HP: A comprehensive set of tools for solving partial differential equations: Diffpack. In: M. Daehlen, A. Tveito (eds). Numerical Methods and Software Tools in Industrial Mathematics. Birkhauser, Boston, MA, 1997, pp 61–90Google Scholar
- 25.Moré J, Sorensen DC, Hillstrom KE, Garbow BS: The MINPACK project. In: W.J. Cowell (ed). Sources and Development of Mathematical Software. Prentice-Hall, 1984Google Scholar