Analysis of Na(+)/Ca (2+) exchanger (NCX) function and current in murine cardiac myocytes during heart failure.

Abstract

Na(+)/Ca(2+) exchanger (NCX) plays important roles in cardiac electrical activity and calcium homeostasis. NCX current (I(NCX)) shows transmural gradient across left ventricle in many species. Previous studies demonstrated that NCX expression was increased and transmural gradient of I(NCX) was disrupted in failing heart, but the mechanisms underlying I(NCX) remodeling still remain unknown. In present study, we used patch clamp technique to record I(NCX) from subepicardial (EPI) myocytes and subendocardial (ENDO) myocytes isolated from sham operation (SO) mice and heart failure (HF) mice. Our results showed that I(NCX) was higher in normal EPI cells compared with that in ENDO, whatever for forward mode or reverse mode. In HF group, I(NCX) was significantly up-regulated, but EPI-ENDO difference was disrupted because of a more increase of I(NCX) in ENDO myocytes. In order to explore the molecular mechanism underlying remodeling of I(NCX) in failing heart, we detected the protein expression of NCX1 and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) by Western blot. We found that CaMKII activity was dramatically enhanced and parallel with the expression of NCX1 in failing heart. Our study demonstrated that transmural gradient of I(NCX) existed in murine left ventricle, and increased activity of CaMKII should account for I(NCX) remodeling in failing heart.

• Authors: Lin Xu, Jing Chen, Xu-Yong Li, Shan Ren, Cong-Xin Huang, Gang Wu, Xiao-Yan Li, Xue-Jun Jiang
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 39 Issue 4 Pg. 3847-52 (Apr 2012) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 21750914 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Sodium-Calcium Exchanger
• sodium-calcium exchanger 1
• Calcium-Calmodulin-Dependent Protein Kinase Type 2

Topics

• Animals
• Body Weight
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Endocardium (pathology)
• Heart Failure (enzymology, pathology, physiopathology)
• Ion Channel Gating
• Male
• Mice
• Mice, Inbred C57BL
• Myocytes, Cardiac (metabolism, pathology)
• Organ Size
• Pericardium (pathology)
• Phosphorylation
• Sodium-Calcium Exchanger (metabolism)