title: Induced overexpression of Na(+)/Ca(2+) exchanger does not aggravate myocardial dysfunction induced by transverse aortic constriction.
abstract: BACKGROUND
  Alterations in expression and activity of cardiac Na(+)/Ca(2+) exchanger (NCX1) have been implicated in the pathogenesis of heart failure.
  
  
  RESULTS
  Using transgenic mice in which expression of rat NCX1 was induced at 5 weeks of age, we performed transverse aortic constriction (TAC) at 8 weeks and examined cardiac and myocyte function at 15-18 weeks after TAC (age 23-26 weeks). TAC induced left ventricular (LV) and myocyte hypertrophy and increased myocardial fibrosis in both wild-type (WT) and NCX1-overexpressed mice. NCX1 and phosphorylated ryanodine receptor expression was increased by TAC, whereas sarco(endo)plasmic reticulum Ca(2+)-ATPase levels were decreased by TAC. Action potential duration was prolonged by TAC, but to a greater extent in NCX1 myocytes. Na(+)/Ca(2+) exchange current was similar between WT-TAC and WT-sham myocytes, but was higher in NCX1-TAC myocytes. Both myocyte contraction and [Ca(2+)](i) transient amplitudes were reduced in WT-TAC myocytes, but restored to WT-sham levels in NCX1-TAC myocytes. Despite improvement in single myocyte contractility and Ca(2+) dynamics, induced NCX1 overexpression in TAC animals did not ameliorate LV hypertrophy, increase ejection fraction, or enhance inotropic (maximal first derivative of LV pressure rise, +dP/dt) responses to isoproterenol.
  
  
  CONCLUSIONS
  In pressure-overload hypertrophy, induced overexpression of NCX1 corrected myocyte contractile and [Ca(2+)](i) transient abnormalities but did not aggravate or improve myocardial dysfunction.
authors.affiliation: Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Jufang
authors.initials: J
authors.lastname: Wang
authors.forename: Erhe
authors.initials: E
authors.lastname: Gao
authors.forename: Tung O
authors.initials: TO
authors.lastname: Chan
authors.forename: Xue-Qian
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Jianliang
authors.initials: J
authors.lastname: Song
authors.forename: Xiying
authors.initials: X
authors.lastname: Shang
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Feldman
authors.forename: Joseph Y
authors.initials: JY
authors.lastname: Cheung
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D004594:Electrophysiology; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011897:Random Allocation; D051381:Rats; D012016:Reference Values; D012680:Sensitivity and Specificity; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*
chemical_list: D019831:Sodium-Calcium Exchanger