Cardiac Ryanodine Receptor Distribution Is Dynamic and Changed by Auxiliary Proteins and Post-Translational Modification
This week we profile a recent publication in eLife from Dr. Parisa Asghari (pictured) the laboratory of Dr. Edwin Moore at UBC.
Can you provide a brief overview of your lab’s current research focus?
The Moore lab is studying the mechanisms which control excitation-contraction coupling in muscle cells.
What is the significance of the findings in this publication?
Dysfunctional intracellular Ca2+ handling mediated via cardiac ryanodine receptors (RyR2) is extremely important in the pathogenesis of atrial fibrillation, heart failure, and inherited rhythm disorders. It is therefore not surprising that RyR2 have been identified as potential therapeutic targets for the treatment of these diseases. Indeed, many exogenous pharmaceutical agents, as well as endogenous hormones and neurotransmitters have been shown to modify RyR2 function. It has been thought that these agents and diseases modulate RyR2 function by altering the gating of the channel, either by changing their sensitivity to Ca2+, controlling the movement of ions through their central pore, or by altering the interaction between the tetramer subunits. In this paper, we have discovered that the distribution of the receptors is dynamic and can be altered by physiological and pathological parameters, and this correlates with changes in their function.
This work was funded by:
Members of the Cardiovascular Research Group in the Life Sciences Institute were funded by the CIHR.