VEGA 2/0116/12

Plasticity of the membrane systems of cardiac myocytes

Principal Investigator: Marta Novotová

Duration: January 2012 – December 2014
Coordinating Organization: Institute of Molecular Physiology and Genetics SAS, Bratislava

Annotation:

In our previous studies, we have shown that cytoarchitecture contributes to intracellular signaling in cardiac myocytes and that cytoarchitectual changes accompany cardiac remodeling. This project aims at characterization of the morphological variability of the sarcolemma and of the sarcoplasmic reticulum with emphasis on the local aspects of excitation-contraction coupling. Changes in the spatial relations of the plasma membrane and of membranes of the sarcoplasmic reticulum will be studied in the mammalian myocardium with the aim to classify and quantify their structural dynamics in the physiologically and pathologically loaded myocardium. Comprehension of the plasticity of the membrane system will be instrumental in understanding of the membrane morphology as the adaptability factor in cardiac myocytes.

Keywords:

Cardiac workload, cardiac myocytes, cytoarchitecture, remodelling

Objectives:

The project is aimed to collect basic knowledge on the membrane plasticity and the ultrastructural dynamics of the membrane systems in mammalian cardiac muscle cells working under normal and pathological conditions. The expected results will help to reveal how the morphology of the cell membrane participates on signaling processes and which structural mechanisms participate in remodeling of the membrane system during adaptation to changes in load.
We will characterize the morphological plasticity of the plasma membrane, its tubular system, of the sarcoplasmic reticulum and its terminal cisterns with emphasis on changes in dyadic microdomains of myocytes of left ventricles and papillary muscles of experimental animals exposed to:

physiological work load
experimentally induced myocardial damage

Publications:

	Huntosova V, Stroffekova K, Wagnieres G, Novotova M, Nichtova Z, Miskovsky P (2014): Endosomes: guardians against [Ru(Phen)] photo-action in endothelial cells during in vivo pO2 detection? Metallomics 6: 2279-2289.
	Caffin F, Prola A, Piquereau J, Novotova M, David DJ, Garnier A, Fortin D, Alavi M, Veksler V, Ventura-Clapier R, Joubert F (2013): Altered skeletal muscle mitochondrial biogenesis but improved endurance capacity in trained OPA1-deficient mice. J Physiol 591: 6017-37.
	Misak A, Grman M, Malekova L, Novotova M, Markova J, Krizanova O, Ondrias K, Tomaskova Z (2013): Mitochondrial chloride channels: electrophysiological characterization and pH induction of channel pore dilation. Eur Biophys J 42: 709-20.
	Piquereau J, Caffin F, Novotova M, Lemaire C, Veksler V, Garnier A, Ventura-Clapier R, Joubert F (2013): Mitochondrial dynamics in the adult cardiomyocytes: which roles for a highly specialized cell? Front Physiol 4: 102.
	Zahradnikova A, Zahradnik I (2012). Construction of calcium release sites in cardiac myocytes. Front Physiol 3: 322.
	Piquereau J, Caffin F, Novotova M, Prola A, Garnier A, Mateo P, Fortin D, Huynh LH, Nicolas V, Alavi MV, Brenner C, Ventura-Clapier R, Veksler V, Joubert F (2012). Down-regulation of OPA1 alters mouse mitochondrial morphology, PTP function, and cardiac adaptation to pressure overload. Cardiovasc Res 94: 408-417.
	Nichtova Z, Novotova M, Kralova E, Stankovicova T (2012): Morphological and functional characteristics of models of experimental myocardial injury induced by isoproterenol. Gen Physiol Biophys 31: 141-51.