Na+-Ca2+ Exchanger Remodeling in Pressure Overload Cardiac Hypertrophy

Zhengyi Wang, Bridgid Nolan, William Kutschke, Joseph A Hill

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Perturbations of Ca2+ metabolism are central to the pathogenesis of cardiac hypertrophy. The electrogenic Na+-Ca 2+ exchanger mediates a substantial component of transmembrane Ca2+ movement in cardiac myocytes and is up-regulated in heart failure. However, the role of the exchanger in the pathogenesis of cardiac hypertrophy is poorly understood. Thoracic aortic banding in mice induced 50-60% increases in heart mass and cardiomyocyte size. Despite the absence of myocardial dysfunction, steady-state NCX1 transcript and protein levels were increased to an extent similar to that reported in heart failure. As recent studies indicate that calcineurin is critical to the expression of Na +-Ca2+ exchanger genes, we inhibited calcineurin with cyclosporin. Calcineurin inhibition blunted the increases in NCX1 transcript and protein levels and eliminated the increases in heart mass and cell volume normally associated with pressure overload. To examine the functional significance of these changes, we measured Na+-Ca2+ exchanger current in two independent ways. Surprisingly, exchanger current density was decreased in hypertrophied myocytes, and this down-regulation was eliminated by calcineurin inhibition. Together, these data reveal a role for Na+-Ca2+ exchanger current in the electrical remodeling of hypertrophy and implicate calcineurin signaling therein. In addition, these data suggest the Na+-Ca2+ exchanger is functionally regulated in hypertrophy.

Original languageEnglish (US)
Pages (from-to)17706-17711
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number21
DOIs
StatePublished - Jan 25 2001

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Calcineurin
Cardiomegaly
Pressure
Cardiac Myocytes
Hypertrophy
Heart Failure
Sodium-Calcium Exchanger
Atrial Remodeling
Cardiac Volume
Cell Size
Metabolism
Muscle Cells
Cyclosporine
Proteins
Current density
Thorax
Down-Regulation
Genes
sodium-calcium exchanger 1

ASJC Scopus subject areas

  • Biochemistry

Cite this

Na+-Ca2+ Exchanger Remodeling in Pressure Overload Cardiac Hypertrophy. / Wang, Zhengyi; Nolan, Bridgid; Kutschke, William; Hill, Joseph A.

In: Journal of Biological Chemistry, Vol. 276, No. 21, 25.01.2001, p. 17706-17711.

Research output: Contribution to journalArticle

Wang, Zhengyi ; Nolan, Bridgid ; Kutschke, William ; Hill, Joseph A. / Na+-Ca2+ Exchanger Remodeling in Pressure Overload Cardiac Hypertrophy. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 21. pp. 17706-17711.
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