Figure 3.
Deranged cardiomyocyte excitation–contraction coupling in heart failure. Intracellular catecholaminergic signal cascades upregulate the phosphorylation state of individual components in an attempt to maintain myocardial inotropy. Despite this, sarcoplasmic reticulum (SR) calcium stores are depleted and the reduced intracellular Ca2+ transient that is generated results in a loss of contractile force. An SR calcium leak through hyperphosphorylated RyR2 also contributes to proarrhythmic conditions.