Compartmentalization in cardiomyocytes modulates creatine kinase and adenylate kinase activities

Rikke Birkedal, Jelena Branovets, Marko Vendelin FEBS Letters 2024 Nov;598(21):2623-2640. PMID: 39112921 DOI: 10.1002/1873-3468.14994 Abstract Intracellular molecules are transported by motor proteins or move by diffusion resulting from random molecular motion. Cardiomyocytes are packed with structures that are crucial for function, but also confine the diffusional spaces, providing cells with a means to control diffusion. They form compartments in which local concentrations ar...
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Published Protocol: Simple Analysis of Gel Images With IOCBIO Gel Software

Lucia Jaska, Rikke Birkedal, Martin Laasmaa, Marko Vendelin Bio-protocol, 2024 Aug 20; 14(16):e5053 PMID: 39210956 DOI: 10.21769/BioProtoc.5053 Abstract Gel image analyses are often difficult to reproduce, as the most commonly used software, the ImageJ Gels plugin, does not automatically record any steps in the analysis process. This protocol provides detailed steps for image analysis using IOCBIO Gel software with western blot as an example; however, the protocol is applic...
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Simple analysis of gel images with IOCBIO Gel

Jaak Kütt, Georg Margus, Lauri Kask, Triinu Rätsepso, Kärol Soodla, Romain Bernasconi, Rikke Birkedal, Priit Järv, Martin Laasmaa, Marko Vendelin BMC Biology 2023 Oct 20;21(1):225 PMID: PMC10589977 DOI: 10.1186/s12915-023-01734-8 Abstract Background: Current solutions for the analysis of Western Blot images lack either transparency and reproducibility or can be tedious to use if one has to ensure the reproducibility of the analysis. Results: Here, we present an open-sou...
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Cardiomyocytes from female compared to male mice have larger ryanodine receptor clusters and higher calcium spark frequency

Martin Laasmaa, Jelena Branovets, Jekaterina Stolova, Xin Shen, Triinu Rätsepso, Mihkel Jaan Balodis, Cärolin Grahv, Eliise Hendrikson, William Edward Louch, Rikke Birkedal, Marko Vendelin The Journal of Physiology, 601(18), 4033–4052 PMID: 37561554 DOI: 10.1113/JP284515 Abstract Sex differences in cardiac physiology are receiving increased attention as it has become clear that men and women have different aetiologies of cardiac disease and require different treatments. The...
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Ontogeny of cardiomyocytes: ultrastructure optimization to meet the demand for tight communication in excitation-contraction coupling and energy transfer

Rikke Birkedal, Martin Laasmaa, Jelena Branovets, Marko Vendelin Philos Trans R Soc Lond B Biol Sci. 2022 Nov 21;377(1864):20210321. PMID: 36189816 DOI: 10.1098/rstb.2021.0321 Abstract The ontogeny of the heart describes its development from the fetal to the adult stage. In newborn mammals, blood pressure and thus cardiac performance are relatively low. The cardiomyocytes are thin, and with a central core of mitochondria surrounded by a ring of myofilaments, while the sarco...
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Altered calcium handling in cardiomyocytes from arginine-glycine amidinotransferase-knockout mice is rescued by creatine

Martin Laasmaa, Jelena Branovets, Karina Barsunova, Niina Karro, Craig A Lygate, Rikke Birkedal, Marko Vendelin Am J Physiol Heart Circ Physiol. 2021 Feb 1;320(2):H805-H825 PMID: 33275525DOI: 10.1152/ajpheart.00300.2020 Abstract The creatine kinase system facilitates energy transfer between mitochondria and the major ATPases in the heart. Creatine-deficient mice, which lack arginine-glycine amidinotransferase (AGAT) to synthesize creatine and homoarginine, exhibit reduced cardiac co...
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Cardiac expression and location of hexokinase changes in a mouse model of pure creatine deficiency

Jelena Branovets, Niina Karro, Karina Barsunova, Martin Laasmaa, Craig A Lygate, Marko Vendelin, Rikke Birkedal Am J Physiol Heart Circ Physiol. 2021 Feb 1;320(2):H613-H629 PMID: 33337958DOI: 10.1152/ajpheart.00188.2020 Abstract Creatine kinase (CK) is considered the main phosphotransfer system in the heart, important for overcoming diffusion restrictions and regulating mitochondrial respiration. It is substrate limited in creatine-deficient mice lacking l-arginine:glycine amidinotr...
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IOCBIO Kinetics: An open-source software solution for analysis of data traces

Marko Vendelin, Martin Laasmaa, Mari Kalda, Jelena Branovets, Niina Karro, Karina Barsunova, Rikke Birkedal PLoS Comput Biol. 2020 Dec 22;16(12):e1008475. PMID: 33351800PMCID: PMC7787677DOI: 10.1371/journal.pcbi.1008475 Abstract Biological measurements frequently involve measuring parameters as a function of time, space, or frequency. Later, during the analysis phase of the study, the researcher splits the recorded data trace into smaller sections, analyzes each section separately b...
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Marker enzyme activities in hindleg from creatine-deficient AGAT and GAMT KO mice – differences between models, muscles, and sexes

Barsunova K, Vendelin M, Birkedal R Sci Rep 2020 May;10(1):7956 PMID: 32409787 Abstract Creatine kinase (CK) functions as an energy buffer in muscles. Its substrate, creatine, is generated by L-arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT). Creatine deficiency has more severe consequences for AGAT than GAMT KO mice. In the present study, to characterize their muscle phenotype further, we recorded the weight of tibialis anterior (TA), extensor digi...
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Cardiac muscle regulatory units are predicted to interact stronger than neighboring cross-bridges

Kalda M, Vendelin M Sci Rep 2020 Mar;10(1):5530 PMID: 32218497 Full text: https://doi.org/10.1038/s41598-020-62452-7 Abstract Model simulations (top) and the scheme showing cooperativity modes Strong interactions between cross-bridges (XB) and regulatory units (RU) lead to a steep response of cardiac muscle to an increase in intracellular calcium. We developed a model to quantitatively assess the influence of different types of interactions within the sarcomere on the prope...
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