Abstract
The ryanodine receptors form the calcium release channel in the membrane of the sarcoplasmic reticulum (SR, the main intracellular Ca2+ store). The importance of ryanodine receptors (RyRs) to cardiac pacemaking and rhythmicity is highlighted by more than 69 mutations, RyR mutations, which underlie arrhythmias and sudden cardiac death. Although most of these mutations lie in cytoplasmic domains, they all cause increased RyR activation by Ca2+ in the SR lumen. Presented here is a review of the mechanisms by which cytoplasmic domains of the RyR can determine luminal activation.
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Acknowledgments
Thanks to Paul Johnson and Katherine Bradley for assisting with the experiments. DRL was supported by a Senior Brawn Fellowship from the University of Newcastle and by infrastructure grant from NSW Health through Hunter Medical Research Institute.
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Proteins, membranes and cells: the structure-function nexus. Contributions from the annual scientific meeting (including a special symposium in honour of Professor Alex Hope of Flinders University, South Australia) of the Australian Society for Biophysics held in Canberra, ACT, Australia, September 28–October 1, 2008.
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Laver, D.R. Luminal Ca2+ activation of cardiac ryanodine receptors by luminal and cytoplasmic domains. Eur Biophys J 39, 19–26 (2009). https://doi.org/10.1007/s00249-009-0417-1
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DOI: https://doi.org/10.1007/s00249-009-0417-1