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This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 297/4/H1263    most recent 00152.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Google Scholar Articles by Schaeffer, P. J. Articles by Kelly, D. P. PubMed PubMed Citation Articles by Schaeffer, P. J. Articles by Kelly, D. P.

Impaired contractile function and calcium handling in hearts of cardiac-specific calcineurin b1-deficient mice

¹Center for Cardiovascular Research, and Department of ²Medicine, Washington University School of Medicine, St. Louis, Missouri Department of ³Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri Department of ⁴Pediatrics, Washington University School of Medicine, St. Louis, Missouri; and ⁵Department of Pharmacology, University of California Davis, Davis, California

Submitted February 13, 2009 ; accepted in final form August 17, 2009

To define the necessity of calcineurin (Cn) signaling for cardiac maturation and function, the postnatal phenotype of mice with cardiac-specific targeted ablation of the Cn B1 regulatory subunit (Ppp3r1) gene (csCnb1^–/– mice) was characterized. csCnb1^–/– mice develop a lethal cardiomyopathy, characterized by impaired postnatal growth of the heart and combined systolic and diastolic relaxation abnormalities, despite a lack of structural derangements. Notably, the csCnb1^–/– hearts did not exhibit diastolic dilatation, despite the severe functional phenotype. Myocytes isolated from the mutant mice exhibited reduced rates of contraction/relaxation and abnormalities in calcium transients, consistent with altered sarcoplasmic reticulum loading. Levels of sarco(endo) plasmic reticulum Ca-ATPase 2a (Atp2a2) and phospholamban were normal, but phospholamban phosphorylation was markedly reduced at Ser¹⁶ and Thr¹⁷. In addition, levels of the Na/Ca exchanger (Slc8a1) were modestly reduced. These results define a novel mouse model of cardiac-specific Cn deficiency and demonstrate novel links between Cn signaling, postnatal growth of the heart, pathological ventricular remodeling, and excitation-contraction coupling.

calcium signaling; restrictive cardiomyopathy; cardiac hypertrophy; excitation-contraction coupling; cardiac mitochondria

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				B. M. Wolska Calcineurin and cardiac function: is more or less better for the heart? Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1576 - H1577. [Full Text] [PDF]