RYANODINE RECEPTOR FUNCTION AND MODULATION
The ryanodine receptor (RyR) is the intracellular Ca2+ channel located in the membrane of sarcoplasmic reticulum (SR) of cardiac cells. Ca2+ entering through L-type Ca2+ channels open the RyR channels, which allow more Ca2+ to be released from intracellular stores in SR. This Ca2+-induced Ca2+ release from SR predominantly contributes to the cytosolic Ca2+ transient that drives the myocardial contraction.
Because of its central role in the cardiac excitation-contraction coupling, the RyR is modulated by many factors including PKA, PP1, PP2A, calmodulin and CaMKII in a macromolecular complex. We study the modulation of RyR activity by phosphorylation during hypertensive disease progression from cardiac hypertrophy to heart failure. We also study the relationship between the RyR cluster spacing and spontaneous Ca2+ wave generation that cause arrhythmias. Our study suggest that in some forms of heart failure, the RyR cluster spacing is shortened, which contributes, in part, to increased propensity of arrhythmias.
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Antibody labeling of RyR2 in cardiac myocyte Y Chen-Izu et al., Biophysical J. 2006. 91:1-13
3D simulation of Ca2+ sparks and waves LT Izu et al., Biophysical J. 2006. 91:95-112