查看文章

Objective: Impaired myocyte Ca²⁺ handling is a common characteristic of failing hearts and increases in calcineurin activity, a Ca²⁺-sensitive phosphatase, have been implicated in heart failure phenotype. Transgenic mice with cardiac-specific expression of an active form of calcineurin display depressed function, hypertrophy and heart failure. We examined whether defects in cardiomyocyte Ca²⁺ handling properties contribute to the impaired cardiac function in calcineurin transgenic mice. Methods: The levels of SR Ca²⁺ handling proteins, SR Ca²⁺ transport function and cardiomyocyte mechanics, as well as Ca²⁺ kinetics were examined in mice overexpressing a constitutively active form of calcineurin. Results: Transgenic expression of activated calcineurin catalytic subunit resulted in significant protein increases (66%) in SERCA2 and decreases (35%) in phospholamban, as well as enhanced (∼80 …