Department of Cellular Cardiology

Research Topic

The research in Department of Cellular Cardiology is focused on sub-cellular mechanisms of cardiac excitation-contraction coupling, the grand topic of cardiac function in health and disease. Our common aim is to contribute to the field by original ideas, to promote internationally competitive research, and to publish in leading journals of the field. Conceptually, we focus on molecular mechanisms of calcium signalling and on ultrastructural aspects of cellular compartments that serve calcium signalling and energetics in myocytes. We used cutting-edge experimental and theoretical methodologies. These include recording, analysis and mathematical modelling of activity of membrane ion channels, of extracellular calcium concentration changes, and of membrane structures.

We use our original experimental techniques of isolation of functional cardiac myocytes, combination of the patch-clamp and confocal microscopy techniques, reconstruction of RYR2 calcium channels in bilayer lipid membranes, quantitative electron microscopy and image analysis. Most of them were supported by our original software for data acquisition and analysis. We developed unique in silico models of RYR2 gating, of calcium release unit and calcium signals, of quantitative 3D ultrastructure of striated muscle cells, all based on our results and on the recent understanding of the topic, which served as effective tools to formulate and verify working hypotheses and to support and to disseminate the results. Find more here: http://confolab.sav.sk/ovsb/en/

Research Team

RNDr. Michal Cagalinec, PhD.

Head of Department

02/ 32295040

Resume

Mgr (2000), RNDr. (2002), PhD (2006)

2016: Senior Research Fellow (IIa), Institute of Experimental Endocrinology, BRC SAS, Bratislava

2018: Head of Department of Cellular Cardiology, Institute of Experimental Endocrinology, BRC SAS, Bratislava

PRINCIPAL INVESTIGATOR:

Ing. Alexandra Zahradníková, DrSc.

RESEARCHERS:

RNDr. Marta Novotová, CSc.

RNDr. Ivan Zahradník, CSc.

RNDr. Alexadra Zahradníková, PhD.

SCIENTIFIC STAFF:

RNDr. Jana Pavelková, CSc.

PhD STUDENTS:

Mgr. Iuliia Baglaeva

Mgr. Bogdan Iaparov

TECHNICAL STAFF:

Gizela Gajdošíková

Ladislav Novota

Publications

  • Koci J, Novotova M, Slavikova M, Klempa B, Zahradnik I (2022). SARS-CoV-2 Exploits Non-Canonical Autophagic Processes to Replicate, Mature, and Egress the Infected Vero E6 Cells. Pathogens 11: 1535. doi: 10.3390/pathogens11121535.
  • Iaparov B, Baglaeva I, Zahradnik I, Zahradnikova A (2022). Magnesium ions moderate calcium-induced calcium release in cardiac calcium release sites by binding to ryanodine receptor activation and inhibition sites. Front Physiol 12: 805956. doi: 10.3389/fphys.2021.805956.
  • Grimbert L, Sanz MN, Gressette M, Rucker-Martin C, Novotova M, Solgadi A, Karoui A, Gomez S, Bedouet K, Jacquet E, Lemaire C, Veksler V, Mericskay M, Ventura-Clapier R, Piquereau JM, Garnier A (2021): Spatiotemporal AMPK alpha 2 deletion in mice induces cardiac dysfunction, fibrosis and cardiolipin remodeling associated with mitochondrial dysfunction in males only. Biol Sex Differ, vol 12: 52. doi: 10.1186/s13293-021-00394-z.
  • Marcek Chorvatova A, Cagalinec M, Chorvat D Jr (2021): Time-resolved imaging of mitochondrial flavin fluorescence and its applications for evaluating the oxidative state in living cardiac cells. Mitochondrial Medicine. Methods in Molecular Biology, vol 2275, chapter 26: 403-414. Humana, New York, NY. Volume 1: Targeting Mitochondria, Weissig V., Edeas M. (eds), ISBN 978-1-0716-1262-0, doi: 10.1007/978-1-0716-1262-0_26.
  • Yin L, Zahradnikova A Jr, Rizzetto R, Boncompani S, Rabesahala de Meritens C, Zhang Y, Joanne P, Marques Sule E, Aguilar-Torres Y, Fernandez-Tenorio M, Villejoubert O, Li L, Wang YY, Mateo P, Nicolas V, Gerbaud P, Lai FA, Perrier R, Alvarez JL, Niggli E, Valdivia HH, Valdivia CR, Ramos-Franco J, Zorio E, Zissimopoulos S, Protasi F, Benitah JP, Gomez AM (2021): Impaired binding to junctophilin2 and nanostructural alteration in CPVT mutation. Circ Res 129: e35-e52, doi: 10.1161/CIRCRESAHA.121.319094.
  • Iaparov B, Zahradnik I, Moskvin AS, Zahradnikova A (2021): In silico simulations reveal that RYR distribution affects the dynamics of calcium release in cardiac myocytes. J Gen Physiol 153: e202012685 doi: 10.1085/jgp.202012685.
  • Kurekova S, Plaas M, Cagalinec M (2020): Short Communication: Lack of functional wolframin causes drop in plasmalemmal sodium-calcium exchanger type 1 expression at early stage in rat model of Wolfram syndrome. Gen Physiol Biophys 39: 499–503 doi: 10.4149/gpb_2020017.
  • Bebarova M, Pasek M, Zahradnik I (2020): Editorial: Toward more accurate data in cardiac cellular electrophysiology. Prog Biophys Mol Biol 157: 1-2 doi: 10.1016/j.pbiomolbio.2020.06.006.
  • Piquereau J, Veksler V, Novotova M, Ventura-Clapier R (2020): Energetic interactions between subcellular organelles in striated muscles. Front Cell Dev Biol 8: 581045 doi: 10.3389/fcell.2020.581045.
  • Iaparov B, Zahradnik I, Moskvin AS, Zahradnikova A (2020): Synergy of calcium release site determinants in control of calcium release events in cardiac myocytes. bioRXiv : doi: https://doi.org/10.1101/2020.08.26.260968.
  • Leskova A, Labajova M, Krausko M, Zahradnikova A Jr, Baluska F, Micieta K, Turňa K, Jasik J (2020): Endosidin 2 accelerates PIN2 endocytosis and disturbs intracellular trafficking of PIN2, PIN3, and PIN4 but not of SYT1. PLoS One 15: e0237448, doi: 10.1371/journal.pone.0237448. eCollection 2020.
  • Selc M, Razga F, Nemethova V, Mazancova P, Ursinyova M, Novotova M, Kopecka K, Gabelova A, Babelova A (2020): Surface coating determines the inflammatory potential of magnetite nanoparticles in murine renal podocytes and mesangial cells. RSC Adv 10: 23916–23929 doi: 10.1039/d0ra03133j.
  • Zahradnikova A, Iaparov B, Zahradnik I (2020): The problem of accuracy in single-channel open probability measurements. Prog Biophys Mol Biol 157: 94-106 doi: 10.1016/j.pbiomolbio.2020.05.00.
  • Novotova M, Zahradnikova A Jr, Nichtova Z, Kovac R, Kralova E, Stankovicova T, Zahradnikova A, Zahradnik I (2020): Structural variability of dyads relates to calcium release in rat ventricular myocytes. Sci Rep 10: 8076 doi: 10.1038/s41598-020-64840-5.
  • Pires Da Silva J, Monceaux K, Guilbert A, Gressette M, Piquereau J, Novotova M, Ventura-Clapier R, Garnier A, Lemaire C (2020): SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy. Cells. 9: E426 doi: 10.3390/cells9020426.
  • Hotka M, Cagalinec M, Hilber K, Hool L, Boehm S, Kubista H (2020): L-type Ca2+ channel-mediated Ca2+ influx adjusts neuronal mitochondrial function to physiological and pathophysiological conditions. Sci Signal. 13: eaaw6923 doi: 10.1126/scisignal.aaw6923.
  • Ebner J, Cagalinec M, Kubista H, Todt H, Szabo PL, Kiss A, Podesser BK, Cserne Szappanos H, Hool LC, Hilber K, Koenig X (2020): Neuronal nitric oxide synthase regulation of calcium cycling in ventricular cardiomyocytes is independent of Cav1.2 channel modulation under basal conditions. Pflugers Arch. 472: 61-74 doi: 10.1007/s00424-019-02335-7.
  • Ďúranová H, Požgajová M, Novotová M, Kňažická Z (2019): Príprava vzoriek z kvasiniek Schizosaccaromyces pombe pre účely transmisnej elektrónovej mikroskopie: review. Recenzovaný zborník vedeckých prác Výskumného centra AgroBioTech 2019 s. 38-44, ISBN 978-80-552-2053-6.
  • Duranova H, Pozgajova M, Novotova M, Lukac N, Knazicka Z (2019): Fission yeast schizosaccharomyces pombe as a model system for ultrastructural investigations using transmission electron microscopy. J Microbiol Biotech Food Sci 9: 160–165 doi: 10.15414/jmbfs.2019.9.1.160-165.
  • Iaparov B, Moskvin AS, Zahradnik I, Zahradnikova A (2019): Stochastic and deterministic approaches to modelling calcium release in cardiac myocytes at different spatial arrangements of ryanodine receptors. Eur Biophys J 48: 579–584 doi: 10.1007/s00249-019-01378-z.
  • Skrabanek P, Zahradnikova A Jr (2019): Automatic assessment of the cardiomyocyte development stages from confocal microscopy images using deep convolutional networks. PLoS One 14: e0216720, doi: 10.1371/journal.pone.0216720.
  • Sramkova M, Kozics K, Masanova V, Uhnakova I, Razga F, Nemethova V, Mazancova P, Kapka-Skrzypczak L, Kruszewski M, Novotova M, Puntes VF, Gabelova A (2019): Kidney nanotoxicity studied in human renal proximal tubule epithelial cell line TH1. Mutat Res 845: 403017 doi: 10.1016/j.mrgentox.2019.01.012.
  • Cagalinec M, Zahradnikova A, Zahradnikova A Jr, Kovacova D, Paulis L, Kurekova S, Hotka M, Pavelkova J, Plaas M, Novotova M, Zahradnik I (2019). Calcium signaling and contractility in cardiac myocyte of wolframin deficient rats. Front Physiol 10: 172, doi: 10.3389/fphys.2019.00172.
  • Ohradanova-Repic A, Machacek C, Donner C, Muhlgrabner V, Petrovcikova E, Zahradnikova A Jr, Vicikova K, Horejsi V, Stockinger H, Leksa V (2019): The mannose 6-phosphate/insulin-like growth factor 2 receptor mediates plasminogen-induced efferocytosisy. J Leukoc Biol. 105: 519-530, doi: 10.1002/JLB.1AB0417-160RR.
  • Safiulina D, Kuum M, Choubey V, Gogichaishvili N, Liiv J, Hickey MA, Cagalinec M, Mandel M, Zeb A, Liiv M, Kaasik A (2019): Miro proteins prime mitochondria for Parkin translocation and mitophagy. EMBO J 38: e99384, doi: 10.15252/embj.201899384.
  • Marcek Chorvatova A, Kirchnerova J, Cagalinec M, Mateasik A, Chorvat D Jr (2019): Spectrally and spatially resolved laser-induced photobleaching of endogenous flavin fluorescence in cardiac myocytes. Cytometry Part A 95: 13-23, doi: 10.1002/cyto.a.23591.
  • Prola A, Nichtova Z, Pires Da Silva J, Piquereau J, Monceaux K, Guilbert A, Gressette M, Ventura-Clapier R, Garnier A, Zahradnik I, Novotova M, Lemaire C (2019): Endoplasmic reticulum stress induces cardiac dysfunction through architectural modifications and alteration of mitochondrial function in cardiomyocytes. Cardiovasc Res 115: 328-342, doi: 10.1093/cvr/cvy197.
  • Martinkova N, Pikula J, Zukal J, Kovacova V, Bandouchova H, Bartonicka T, Botvinkin AD, Brichta J, Dundarova H, Kokurewicz T, Irwin NR, Linhart P, Orlov OL, Piacek V, Skrabanek P, Tiunov MP, Zahradnikova A Jr (2018): Hibernation temperature-dependent Pseudogymnoascus destructans infection intensity in Palearctic bats. Virulence 9: 1734-1750.
  • Harazim M, Horacek I, Jakesova L, Luermann K, Moravec JC, Morgan S, Pikula J, Sosik P, Vavrusova Z, Zahradníková A Jr, Zukal J, Martinkova N (2018): Natural selection in bats with historical exposure to white-nose syndrome. BMC Zoology 3: 8.
  • Bandouchova H, Bartonicka T, Berkova H, Brichta J, Kokurewicz T, Kovacova V, Linhart P, Piacek V, Pikula J, Zahradníková A Jr, Zukal J (2018): Alterations in the health of hibernating bats under pathogen pressure. Sci Rep 8: 6067.
  • Zahradníková A Jr, Kovacova V, Martinkova N, Orlova MV, Orlov OL, Piacek V, Zukal J, Pikula J (2018): Historic and geographic surveillance of Pseudogymnoascus destructans possible from collections of bat parasites. Transbound Emerg Dis 65: 303-308.
  • Hotka M, Zahradnik I (2017): Reconstruction of membrane current by deconvolution and its application to membrane capacitance measurements in cardiac myocytes. PLoS One 12: e0188452.
  • Wang YY, Mesirca P, Marques-Sule E, Zahradnikova A Jr, Villejoubert O, D’Ocon P, Ruiz C, Domingo D, Zorio E, Mangoni ME, Benitah JP, Gómez AM (2017). RyR2R420Q catecholaminergic polymorphic ventricular tachycardia mutation induces bradycardia by disturbing the coupled clock pacemaker mechanism. JCI Insight 2: e91872.
  • Faltinova A, Tomaskova N, Antalik M, Sevcik J, Zahradnikova A (2017). The N-terminal region of the ryanodine receptor affects channel activation. Front Physiol 8: 443.
  • Ragni CV, Diguet N, Le Garrec JF, Novotova M, Resende TP, Pop S, Charon N, Guillemot L, Kitasato L, Badouel C, Dufour A, Olivo-Marin JC, Trouvé A, McNeill H, Meilhac SM. (2017): Amotl1 mediates sequestration of the Hippo effector Yap1 downstream of Fat4 to restrict heart growth. Nat Commun 27: 14582.
  • Huntosova V, Novotova M, Nichtova Z, Balogova L, Maslanakova M, Petrovajova D, Stroffekova K (2017): Assessing light-independent effects of hypericin on cell viability, ultrastructure and metabolism in human glioma and endothelial cells. Toxicol In Vitro 40: 184–195.