The location of energetic compartments affects energetic communication in cardiomyocytes

Birkedal R, Laasmaa M, Vendelin M Front Physiol 2014;5:376 PMID: 25324784 Full text: http://dx.doi.org/10.3389/fphys.2014.00376 Abstract The heart relies on accurate regulation of mitochondrial energy supply to match energy demand. The main regulators are Ca(2+) and feedback of ADP and Pi. Regulation via feedback has intrigued for decades. First, the heart exhibits a remarkable metabolic stability. Second, diffusion of ADP and other molecules is restricted specifically in heart an...
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Tight coupling of Na+/K+-ATPase with glycolysis demonstrated in permeabilized rat cardiomyocytes

Sepp M, Sokolova N, Jugai S, Mandel M, Peterson P, Vendelin M PLoS ONE 2014;9(6):e99413 PMID: 24932585 Abstract The effective integrated organization of processes in cardiac cells is achieved, in part, by the functional compartmentation of energy transfer processes. Earlier, using permeabilized cardiomyocytes, we demonstrated the existence of tight coupling between some of cardiomyocyte ATPases and glycolysis in rat. In this work, we studied contribution of two membrane ATPases and w...
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ADP protects cardiac mitochondria under severe oxidative stress

Sokolova N, Pan S, Provazza S, Beutner G, Vendelin M, Birkedal R, Sheu SS PLoS ONE 2013;8(12):e83214 PMID: 24349464 Abstract ADP is not only a key substrate for ATP generation, but also a potent inhibitor of mitochondrial permeability transition pore (mPTP). In this study, we assessed how oxidative stress affects the potency of ADP as an mPTP inhibitor and whether its reduction of reactive oxygen species (ROS) production might be involved. We determined quantitatively the effects of ...
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Unchanged mitochondrial organization and compartmentation of high-energy phosphates in creatine-deficient GAMT-/- mouse hearts

Branovets J, Sepp M, Kotlyarova S, Jepihhina N, Sokolova N, Aksentijevic D, Lygate CA, Neubauer S, Vendelin M, Birkedal R Am. J. Physiol. Heart Circ. Physiol. 2013 Aug;305(4):H506-20 PMID: 23792673   Abstract Disruption of the creatine kinase (CK) system in hearts of CK-deficient mice leads to changes in the ultrastructure and regulation of mitochondrial respiration. We expected to see similar changes in creatine-deficient mice, which lack the enzyme guanidinoacetate methyltr...
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Real-time determination of sarcomere length of a single cardiomyocyte during contraction

Peterson P, Kalda M, Vendelin M Am. J. Physiol., Cell Physiol. 2013 Mar;304(6):C519-31 PMID: 23255581 Abstract Sarcomere length of a cardiomyocyte is an important control parameter for physiology studies on a single cell level; for instance, its accurate determination in real time is essential for performing single cardiomyocyte contraction experiments. The aim of this work is to develop an efficient and accurate method for estimating a mean sarcomere length of a contracting cardiomy...
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Sensitivity analysis of flux determination in heart by H₂ ¹⁸O -provided labeling using a dynamic Isotopologue model of energy transfer pathways

Schryer DW, Peterson P, Illaste A, Vendelin M PLoS Comput. Biol. 2012;8(12):e1002795 PMID: 23236266 Abstract To characterize intracellular energy transfer in the heart, two organ-level methods have frequently been employed: ³¹P − NMR inversion and saturation transfer, and dynamic ¹⁸O labeling. Creatine kinase (CK) fluxes obtained by following oxygen labeling have been considerably smaller than the fluxes determined by ³¹P − NMR saturation transfer. It has been proposed that dynamic ¹...
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Analysis of molecular movement reveals latticelike obstructions to diffusion in heart muscle cells

Illaste A, Laasmaa M, Peterson P, Vendelin M Biophys. J. 2012 Feb;102(4):739-48 PMID: 22385844 Abstract Intracellular diffusion in muscle cells is known to be restricted. Although characteristics and localization of these restrictions is yet to be elucidated, it has been established that ischemia-reperfusion injury reduces the overall diffusion restriction. Here we apply an extended version of raster image correlation spectroscopy to determine directional anisotropy and coefficients ...
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Molecular dynamics simulations of creatine kinase and adenine nucleotide translocase in mitochondrial membrane patch

Karo J, Peterson P, Vendelin M J. Biol. Chem. 2012 Mar;287(10):7467-76 PMID: 22241474 Abstract Interaction between mitochondrial creatine kinase (MtCK) and adenine nucleotide translocase (ANT) can play an important role in determining energy transfer pathways in the cell. Although the functional coupling between MtCK and ANT has been demonstrated, the precise mechanism of the coupling is not clear. To study the details of the coupling, we turned to molecular dynamics simulations. We ...
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Permeabilized rat cardiomyocyte response demonstrates intracellular origin of diffusion obstacles

Jepihhina N, Beraud N, Sepp M, Birkedal R, Vendelin M Biophys. J. 2011 Nov;101(9):2112-21 PMID: 22067148 Abstract Intracellular diffusion restrictions for ADP and other molecules have been predicted earlier based on experiments on permeabilized fibers or cardiomyocytes. However, it is possible that the effective diffusion distance is larger than the cell dimensions due to clumping of cells and incomplete separation of cells in fiber preparations. The aim of this work was to check...
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Application of regularized Richardson-Lucy algorithm for deconvolution of confocal microscopy images

Laasmaa M, Vendelin M, Peterson P J Microsc 2011 Aug;243(2):124-40 PMID: 21323670 Abstract Although confocal microscopes have considerably smaller contribution of out-of-focus light than widefield microscopes, the confocal images can still be enhanced mathematically if the optical and data acquisition effects are accounted for. For that, several deconvolution algorithms have been proposed. As a practical solution, maximum-likelihood algorithms with regularization have been used. Howe...
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