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Calcium transient in cardiomyocytes is regulated by multiple protein kinases and phosphatases. PP2A is a major protein phosphatase in the heart modulating Ca 2+  handling through an array of ion channels, antiporters and pumps, etc. The assembly, localization/translocation, and substrate specificity of PP2A are controlled by different post-translational mechanisms, which in turn are linked to the activities of upstream signaling molecules. Abnormal PP2A expression and activities are associated with defective response to β-adrenergic stimulation and are indication and causal factors in arrhythmia and heart failure.

Regulation of Ca2+ transient by PP2A in normal and failing heart