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Cardiovascular disease is a leading cause of death worldwide. Arrhythmias are associated with significant morbidity and mortality related to cardiovascular disease. Recent work illustrates that many cardiac arrhythmias are initiated by a pathologic imbalance between kinase and phosphatase activities in excitable cardiomyocytes.

To test the relationship between myocyte kinase/phosphatase imbalance and cellular and whole animal arrhythmia phenotypes associated with ankyrin-B cardiac syndrome.

By using a combination of biochemical, electrophysiological, and in vivo approaches, we tested the ability of calcium/calmodulin-dependent kinase (CaMKII) inhibition to rescue imbalance in kinase/phosphatase pathways associated with human ankyrin-B-associated cardiac arrhythmia.

The cardiac ryanodine receptor (RyR₂), a validated target of kinase …