VEGA 2/0197/11

Principal Investigator: Alexandra Zahradníková, jr., Jana Pavelková

Duration: January 2011 – December 2013
Coordinating Organization: Institute of Molecular Physiology and Genetics SAS, Bratislava

Annotation:

Robustness of excitation-contraction coupling in cardiomyocytes is locally ensured by the presence of a large number of DHPR and RyR channels in the dyad. Significant redundancy of the system allows, if necessary, to recruit more channels and thus continuously respond to the increased contractions. This project aims to study the mechanism of interaction between DHPR and RyR channels, mediated by calcium ions, in the cardiomyocytes in situ. We will use a combination of two modern experimental techniques. Voltage clamp method allows us to track response of DHPR channels to voltage stimulus and measure the calcium current value that is a stimulus activating the RyR channels. The method of confocal microscopy enables us to trace the local release of calcium via RyR channels and thereby directly measure their activity in situ. This project will help us understand better the mechanisms regulating communication between the DHPR and RyR channels, and allow us to study the changes of these mechanisms occurring during.

Keywords:

Calcium signalling, excitation-contraction coupling, cardiomyocytes, calcium current, ryanodine receptors

Objectives:

The project aims to further understanding of mechanisms of interaction between DHPR and RyR channels, conveyed by calcium ions, in dyads of cardiomyocytes. The questions that we specifically adress are:

• In what manner does the stimulating calcium affect the rate and amplitude of the local calcium release?
• To what extents are the fast and slow inactivation of calcium current dependent on the rate and amplitude of local calcium release?
• Which intracellular regulators of RyR channel activity are mostly involved in the modulation of the local calcium release?

Publications: