Molecular Physiology // Science

Heart muscle can grow during most of the lifespan and it has significant capability of adaptation and plasticity. An increase in the work load (preload and/or afterload) and activity (heart rate) control the growth and properties of the muscle cells. The triggers for the adaptation are believed to be changes in the activities of ion channels acting in concert with complex calcium signaling mechanisms of the cells. These mechanisms form the basis of the extreme plasticity of cardiac muscle. Cardiomyocyte plasticity is manifested especially well during cardiac organogenesis and during the development of cardiac failure.

Specific projects

  • Patient derived iPS cells as a model of genetic hypertrophic cardiomyopathies
  • Role of specific PGC1α isoforms in cardiac physiology and energy metabolism
  • Mitochondrial complex I inhibitor protein NDUFA4L2 as a regulator of cardiac energy metabolism
  • Molecular events behind cardiac adaptation to hypoxia
  • Mechanisms initiating and regulating function of cardiac muscle cells during development

Methods

  • In vitro cell culture models
    • Primary cultures of isolated mouse cardiomyocytes
    • Cardiomyocytes derived from patient specific human induced pluripotent stem cells
  • Gene and biotechnological methods (e.g. western blot, cell transfection procedures)
  • Electrophysiological analysis (e.g. patch clamp), calcium imaging with confocal microscope
  • Assessment of energy metabolism with Seahorse Extracellular Flux Analyzer

  • Ex vivo tissue model
    • Langendorf perfusion of isolated heart
  • In vivo animal models
  • Mouse models of cardiac ischemia and load-induced cardiac hypertrophy
  • Several different transgenic mouse models
  • Echocardiographic and immunohistological analysis
  • In silico modeling
    • Integrated mathematical models for cardiomyocyte excitation contraction coupling

Collaborations

At UEF

  • Jari Koistinaho, A.I. Virtanen Institute for Molecular Sciences; human induced pluripotent stem cells
  • Anna-Liisa Levonen, A.I. Virtanen Institute for Molecular Sciences; animal models
  • Seppo Ylä-Herttuala, A.I. Virtanen Institute for Molecular Sciences; virus vectors
  • Merja Heinäniemi, Institute of Biomedicine; bioinformatics
  • Jorma Palvimo, Institute of Biomedicine; chromatin immunoprecipitation, genomics
  • Johanna Kuusisto, Kuopio University Hospital; patient material from heart failure patients
  • Markku Laakso, Kuopio University Hospital; genetics of inherited heart diseases
  • Kati Hanhineva, LS-MC Metabolomics Center; mass spectrometry

Outside University

  • Johanna Lanner, Karolinska Institutet
  • Jorge Ruas, Karolinska Institutet
  • Håkan Westerblad, Karolinska Institutet
  • Kari Alitalo, University of Helsinki
  • Heikki Ruskoaho, University of Helsinki
  • William Louch, University of Oslo
  • Thomas Jespersen, University of Copenhagen
  • Morten Thomsen, University of Copenhagen
  • Jennifer Estall, Institut de recherches cliniques de Montréal

Selected publications

  • Karppinen S, Rapila R, Naumenko N, Tuomainen T, Koivumäki JT, Hänninen SL, Korhonen T, Tavi P. Ca(2+) -activated K(+) current is essential for maintaining excitability and gene transcription in early embryonic cardiomyocytes. Acta Physiol (Oxf). 2016 Jan;216(1):101-11.
  • Puttonen KA, Ruponen M, Naumenko N, Hovatta OH, Tavi P, Koistinaho J. Generation of Functional Neuromuscular Junctions from Human Pluripotent Stem Cell Lines. Front Cell Neurosci. 2015 Dec 8;9:473.
  • Holopainen T, Räsänen M, Anisimov A, Tuomainen T, Zheng W, Tvorogov D, Hulmi JJ, Andersson LC, Cenni B, Tavi P, Mervaala E, Kivelä R, Alitalo K. Endothelial Bmx tyrosine kinase activity is essential for myocardial hypertrophy and remodeling. Proc Natl Acad Sci U S A. 2015 Oct 20;112(42):13063-8.
  • Kuosmanen SM, Hartikainen J, Hippeläinen M, Kokki H, Levonen AL, Tavi P. MicroRNA profiling of pericardial fluid samples from patients with heart failure. PLoS One. 2015 Mar 12;10(3):e0119646.
  • Louch WE, Koivumäki JT, Tavi P. Calcium signalling in developing cardiomyocytes: implications for model systems and disease. J Physiol. 2015 Mar 1;593(5):1047-63.
  • Koivumäki JT, Seemann G, Maleckar MM, Tavi P. In silico screening of the key cellular remodeling targets in chronic atrial fibrillation. PLoS Comput Biol. 2014 May 22;10(5):e1003620.
  • Ronkainen VP, Tuomainen T, Huusko J, Laidinen S, Malinen M, Palvimo JJ, Ylä-Herttuala S, Vuolteenaho O, Tavi P. Hypoxia-inducible factor 1-induced G protein-coupled receptor 35 expression is an early marker of progressive cardiac remodelling. Cardiovasc Res. 2014 Jan 1;101(1):69-77.
  • Korhonen T, Rapila R, Tavi P. Mathematical model of mouse embryonic cardiomyocyte excitation-contraction coupling. J Gen Physiol. 2008 Oct;132(4):407-19.