APVV-LPP-0441-09

Mechanisms of ryanodine receptor dysregulation

Principal Investigator: Alexandra Zahradníková

Duration: January 2009 – December 2012
Coordinating Organization: Institute of Molecular Physiology and Genetics SAS, Bratislava

Annotation:

Contraction of cardiac muscle is evoked by calcium release from intracellular stores into the cytoplasm. In a healthy cardiac myocyte, massive calcium release occurs only during the systole in response to processes that follow membrane depolarization. Due to increased calcium release during the diastole that occurs in many cardiac diseases, calcium contents of the stores and systolic contraction are decreased, while the propensity to massive spontaneous calcium release, delayed afterdepolarizations and arrhythmias is increased. The scientific objective of this project is to elucidate the regulation mechanisms of diastolic calcium release via the calcium release channel (RyR), and to define the effects of changes in RyR gating on calcium handling and calcium signaling in the cardiac myocyte. These studies will enable to identify defects of calcium handling in cardiac disease.
The pedagogical objective of this proposal is to prepare one PhD student for her profession so that she is able to fully employ her talents and find an appropriate career. After obtaining PhD she should be able to find a postdoctoral position in a prestigious laboratory and complete her postdoctoral stay productively. Alternatively, they should be able to get a position outside academia in which she could fully use her knowledge, skills and creativity.

Keywords:

Calcium handling, calcium signaling, ventricular myocyte, ryanodine receptor, electrophysiology, mathematical modeling, cardiac disease

Objectives:

The objective of the project is to elucidate molecular mechanisms of ryanodine receptor regulation during the diastole and to determine the consequences of defective ryanodine receptor modulation on spontaneous diastolic calcium release and excitation-contraction coupling in cardiac diseases. The pedagogical objective is to prepare one PhD student for a successful career.

Publications:

	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.
	Faltinova A, Zahradnikova A (2013): Modification of cardiac RYR2 gating by a peptide from the central domain of the RYR2. Cent Eur J Biol 8: 1164-1171.
	Bauerova-Hlinkova V,Bauer J, Hostinova E, Gasperik J, Beck K, Borko L, Faltinova A, Zahradnikova A, Sevcik J (2011): Bioinformatics Domain Structure Prediction and Homology Modeling of Human Ryanodine Receptor 2. Editor Mahmood A. Mahdavi. In Bioinformatics-Trends and Methodologies. – Rijeka, p. 325-352. ISBN 978-953-307-282-1.