Background: PP2A is a regulator of cardiac excitation-contraction coupling. Results: Cardiomyocyte-directed overexpression of B56␣, the main cardiac PP2A regulatory subunit, results in the dephosphorylation of myofilament proteins, increased Ca 2ϩ sensitivity, and higher contractility. Conclusion: This suggests an important role for B56␣ in regulating PP2A activity and thereby the contractile function. Significance: PP2A-B56␣ is a potential pharmacological target to improve cardiac performance in failing hearts.

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