Moreover, in heart failure of various etiologies, RyR2 hyper-phosphorylation has been observed in parallel with increased RyR open probability, calcium sensitivity, spark frequency, or diastolic calcium release (Marx et al., 2000; Okuda et al., 2018), and these effects were at least in part caused by changes in Mg2+ regulation of RyRs (Li et al., 2013). This evidence concerns the gene RYR2 and heart failure.