A paper by Yasmin Hashambhoy, Joseph Greenstein, and Raimond Winslow has been selected for inclusion in a Virtual Special Issue of the Journal of Molecular and Cellular Cardiology on Calcium “enclosing a selection of outstanding contributions on the topic published over the past two years”. The paper selected is “Role of CaMKII in RyR leak, EC coupling and action potential duration: A computational model”, and was originally published in JMCC 49:4, October 2010.

To summarize, “Experimental evidence shows that increased Ca/calmodulin-dependent kinase II (CaMKII) activity is linked with SR Ca leak, a hallmark of heart failure. However, CaMKII has many different intracellular targets, and it is unclear exactly how it contributes to disease. In order to address this question, we constructed a carefully constrained stochastic model of CaMKII and its closely apposed targets in the cardiac dyad, L-type Ca channels (LCCs) and ryanodine receptors (RyRs). Our results predicted that CaMKII hyperphosphorylation of LCCs can lead to early after depolarizations (EADs) and that phosphorylation of LCCs has a greater effect on SR Ca leak than direct phosphorylation of RyRs.”