The type-2 cardiac ryanodine receptor (RyR2) is a Ca2+-activated Ca2+ ion channel located in the junctional sarcoplasmic reticulum (jSR) whose primary function is to regulate the amount, and the rate, of Ca2+ released from the jSR. Ca2+ release is the primary determinant of cardiac contractile force. Each jSR is decorated with between one and several hundred RyR2 that affect each other’s open probability through Ca2+-induced Ca2+ release (CICR) and through allosteric interactions. Recent and exciting data from the lab has shown that RyR2 channels are mobile and can interact with their neighbours in multiple ways. The interactions are dynamic and dependent on post-translational modifications and ligands. This opens an unprecedented higher-level type of regulation, whereby the activity of RyR2, and hence the amount of Ca2+ released, could be dictated by making and breaking allosteric coupling between RyR2 channels.

We are investigating RyR2 position and function in both normal and diseased tissue using a variety of cutting-edge and established techniques, including transmission electron microscopy, electron tomography, confocal and deconvolution microscopy, 3D superresolution immunofluorescence microscopy, transgenic mice, Ca2+ spark and Ca2+ transient analyses as well as biochemical approaches.

  1. Tafteh R, Scriven DRL, Moore EDW, Chou KC. (2015) Single molecule localization deep within thick cells; a novel super resolution microscopeJournal of Biophotonics. [IF 4.45].
  2. Scriven DRL, Moore EDW*. (2014) The dynamic dyad: cardiac ryanodine receptors on the move. Receptors and Clinical Investigation 1:322-324.
  3. Asghari P, Scriven DR, Sanatani S, Gandhi SK, Campbell AI, Moore ED(2014) Non-Uniform and Variable Arrangements of Ryanodine Receptors Within Mammalian Ventricular CouplonsCirculation Research 115: 252-262. [IF 11.10].
  4. Scriven DRL, Asghari P, Moore EDW* (2013) Microarchitecture of the Dyad. Cardiovascular Research 98:169-176. [IF 5.94].
  5. Scriven DRL, Moore, EDW*. (2013) Ca2+ Channel and Na+/Ca2+ Exchange Localization in Cardiac Myocytes. Journal of Molecular and Cellular Cardiology 58:22-31. [IF 5.04].
  6. Asghari P, Scriven DRL, Hoskins J, Fameli N, van Breemen C, Moore EDW*. (2012) The Structure and Functioning of the Couplon in Mammalian Cardiomyocytes. Protoplasma 249 (S1): S31-S38. [IF 3.17].
  7. Bround MJ, Asghari P, Wambolt RB, Bohunek L, Smits C, Philit M, Kieffer TJ, Lakatta EG, Boheler KR, Moore ED, Allard MF, Johnson JD. (2012) Cardiac ryanodine receptors control heart rate and rhythmicity in adult mice. Cardiovascular Research 96:372-380. [IF 5.94].
  8. Schulson MN, Fletcher P, Scriven DRL, Moore EDW*. (2011) Couplons in rat atria form distinct sub-groups defined by their molecular partners. Cell Science 124: 1167-1174. [IF 5.33].
  9. Fletcher PA, Scriven DRL, Schulson MN, Moore EDW*. (2010) Multi-Image Colocalization and its Statistical Significance. Biophysical Journal 99: 1996-2005. [IF 4.22].
  10. Scriven DRL, Asghari P, Schulson MN, Moore EDW*. (2010) Analysis of Cav 1.2 and Ryanodine Receptor Clusters in Rat Ventricular MyocytesBiophysical Journal 99: 3923-3929. IF 4.22].
  11. Perkins AD, Shamsian A, Asghari P, Ellis SJ, Ng LCT, Moore EDWTanentzapf G. (2010) Integrin-mediated adhesion maintains the sarcomeric cytoarchitecture. Developmental Biology 338(1): 15-27. [IF 4.09].
  12. Schubert P, Thon JN, Walsh GM, Chen CH, Moore ED, Devine DV, Kast J. (2009) A signalling pathway contributing to platelet storage lesion development: targeting PI3-kinase-dependent Rap1 activation slows storage-induced platelet deterioration. Transfusion 49: 1944-55. [IF 2.98].
  13. Chopra N, Yang T, Asghari P, Moore ED, Huke S, Akin B, Cattolica RA, Perez CF, Hlaing, T, Knollmann-Ritschel BE, Jones LR, Pessah IN, Allen PD, Franzini-Armstrong C, Knollmann BC. (2009) Ablation of triadin causes loss of cardiac Ca2+ release units, impaired excitation-contraction coupling, and cardiac arrhythmias. Proceedings of the National Academy of Sciences USA 106: 7636-41. [IF 10.23].
  14. Asghari P, Schulson M, Scriven DR, Martens G, Moore ED*. (2009) Axial tubules of rat ventricular myocytes form multiple junctions with the sarcoplasmic reticulum. Biophysical Journal 96: 4651-60. [IF 4.39].
Further publications can be found here.
Lab Members

Parisa Asghari, PhDDavid Scriven, PhD

Myles Ng, BSc candidate

Borna Naderi, BSc candidate