Determinants of coupled gating among cardiac ryanodine receptors
Principal Investigator: Marta Gaburjáková
Duration: January 2011 – December 2013
In the heart, the contraction occurs in response to a small influx of Ca2+ into the myocyte that causes the opening of ryanodine receptors (RyR) and the release of a much larger amount of Ca2+ from the intracellular stores. This process displays an intrinsic positive feedback of released Ca2+ on further release; therefore, a termination mechanism must exist to ensure rhythmic cardiac activity. Coupled gating of RyR channels, one candidate for a shutting mechanism, is manifested by synchronic operation of several RyR channels. The simultaneous closure of all RyR channels in a release unit would break the positive feedback loop and terminate the Ca2+ release. The objective of our work is to identify determinants of coupled gating phenomenon in order to understand the mechanism of inter-channel communication. We will employ the method of ion channel reconstitution into planar lipid membrane that provides detail information about the channel function by recording the current running via the channel pore.
|Tencerová B, Zahradníková A, Gaburjáková J, and Gaburjáková M (2012): Luminal Ca2+ controls activation of the cardiac ryanodine receptor by ATP. J Gen Physiol 140:93-108.|
|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.|