VEGA 2/0143/17

Diastolic function of the ryanodine receptor and generation of arrhythmogenic calcium waves

Principal Investigator: Alexandra Zahradníková

Duration: January 2017 – December 2019
Coordinating Organization: Institute of Molecular Physiology and Genetics SAS, Bratislava

Annotation:

In some acquired and genetic arrhythmias, anomalies in calcium release occur during the diastole, which may result in formation of calcium waves that initiate cardiac arrhythmias. Proper diastolic function of the system of calcium homeostasis involves regulation of diastolic calcium release by ryanodine receptors. Anomalous calcium release from the viewpoint of calcium wave formation is not sufficiently understood. We will concentrate on determination of the relationships between localization of dyads as the sites of calcium release and formation of calcium waves, and on their development during maturation and physiological hypertrophy of myocytes. The outcome of the project will be a better understanding of the factors governing calcium homeostasis in cardiac myocytes and their impairment leading to calcium waves.

Keywords:

Myocardium, myocyte, calcium homeostasis, calcium signalling, ryanodine receptor, super- resolution STED microscopy, mathematical modelling

Objectives:

The overall objective of the project is to characterize regulation of diastolic RyR activity during ontogenesis and physiological hypertrophy. To reach this goal we have formulated the following specific aims:

To obtain quantitative data on formation of calcium waves during cardiomyocyte maturation and physiological hypertrophy and on possible pharmacological intervention
To obtain quantitative data on localization and environment of dyads – calcium release sites – during maturation and physiological hypertrophy of cardiac myocytes
To assess the relationship between localization and environment of dyads and the propensity of myocytes to generation of calcium waves.

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.