Respiration of permeabilized cardiomyocytes from mice: no sex differences, but substrate-dependent changes in the apparent ADP-affinity

Karro N, Laasmaa M, Vendelin M, Birkedal R Sci Rep 2019 Aug;9(1):12592 PMID: 31467353 Abstract Sex differences in cardiac physiology are getting increased attention. This study assessed whether isolated, permeabilized cardiomyocytes from male and female C57BL/6 mice differ in terms of their respiration with multiple substrates and overall intracellular diffusion restriction estimated by the apparent ADP-affinity of respiration. Using respirometry, we recorded 1) the activities of respiratory...
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IOCBIO Sparks detection and analysis software

Laasmaa M, Karro N, Birkedal R, Vendelin M. PeerJ. 2019 Mar 29;7:e6652 PMID: 30956900 Full text: https://doi.org/10.7717/peerj.6652 Abstract Analysis of calcium sparks in cardiomyocytes can provide valuable information about functional changes of calcium handling in health and disease. As a part of the calcium sparks analysis, sparks detection and characterization is necessary. Here, we describe a new open-source platform for automatic calcium sparks detection from line ...
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Revealing calcium fluxes by analyzing inhibition dynamics in action potential clamp

Laasmaa M, Birkedal R, Vendelin M J. Mol. Cell. Cardiol. Volume 100, November 2016, Pages 93–108 PMID: 27702573 Full text: http://doi.org/10.1016/j.yjmcc.2016.08.015 Abstract In cardiac excitation-contraction coupling (ECC), calcium enters the cytosol via L-type Ca2+ channels (LTCC) and reverse Na+/Ca2+-exchange (NCXrev), or is released from the sarcoplasmic reticulum (SR) by Ca2+-induced Ca2+-release (CICR). The magnitude of Ca2+ influx via the different pathways varies with the ...
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Metabolic compartmentation in rainbow trout cardiomyocytes: coupling of hexokinase but not creatine kinase to mitochondrial respiration

Karro N, Sepp M, Jugai S, Laasmaa M, Vendelin M, Birkedal R J. Comp. Physiol. B, Biochem. Syst. Environ. Physiol. 2016 Aug; PMID: 27522222 Full text: http://doi.org/10.1007/s00360-016-1025-x Abstract Rainbow trout (Oncorhynchus mykiss) cardiomyocytes have a simple morphology with fewer membrane structures such as sarcoplasmic reticulum and t-tubules penetrating the cytosol. Despite this, intracellular ADP diffusion is restricted. Intriguingly, although diffusion is restricted, trout cardiom...
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Restricted ADP movement in cardiomyocytes: Cytosolic diffusion obstacles are complemented with a small number of open mitochondrial voltage-dependent anion channels

Simson P, Jepihhina N, Laasmaa M, Peterson P, Birkedal R, Vendelin M J. Mol. Cell. Cardiol. Volume 97, August 2016, Pages 197–203; PMID: 27261153 Full text: http://doi.org/10.1016/j.yjmcc.2016.04.012 Abstract Adequate intracellular energy transfer is crucial for proper cardiac function. In energy starved failing hearts, partial restoration of energy transfer can rescue mechanical performance. There are two types of diffusion obstacles that interfere with energy transfer from mit...
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Cross-Bridge Group Ensembles Describing Cooperativity in Thermodynamically Consistent Way

Kalda M, Peterson P, Vendelin M PLoS ONE 2015;10(9):e0137438 PMID: 26361396 Full text: http://doi.org/10.1371/journal.pone.0137438 Abstract The aim of this work is to incorporate cooperativity into Huxley-type cross-bridge model in thermodynamically consistent way. While the Huxley-type models assume that cross-bridges act independently from each other, we take into account that each cross-bridge is influenced by its neighbors and cooperativity is induced by tropomyosin movement. For that...
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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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