Competition between Ca2+ and other cation for luminally located binding site on the cardiac ryanodine receptor and its effect on the receptor regulation
Principal Investigator: Jana Gaburjáková
Duration: January 2012 – December 2014
The key determinant of cardiac contractility is Ca2+ released from the sarcoplasmic reticulum (SR) via cardiac ryanodine receptor type 2 (RyR2) that is localized in membrane of the SR. The cytoplasmic domain of the channel has been considered to be the main regulatory region. However, also smaller luminal part contributes to the channel regulation. It has been shown that different divalent cations interact with cytosolic channel activation site (A-site) and compete for binding, thus cytosolic regulation of the channel can be modified. The dominant regulatory ion in the lumen of SR is Ca2+ but Mg2+ is also present. Both ions bind to the luminally located interaction site (L-site) of the RyR2 channel and compete for binding. This could potentially affect the luminal regulation of the RyR2 channel. Our main aim is to perform a comprehensive study of cation competition on luminal face of the RyR2 channel in order to better understand luminal regulation of the RyR2 channel under physiological conditions.
|Gaburjakova M, Bal NC, Gaburjakova J, Periasamy M (2013): Functional interaction between calsequestrin and ryanodine receptor in the heart. Cell Mol Life Sci 70: 2935-2945.
|Gaburjakova J, Gaburjakova M (2014): Coupled gating modifies the regulation of cardiac ryanodine receptors by luminal Ca2+. Biochim Biophys Acta – Biomembranes 1838:867-873.