title: The Na+/Ca2+ exchanger/SR Ca2+ ATPase transport capacity regulates the contractility of normal and hypertrophied feline ventricular myocytes.
abstract: BACKGROUND
  Pressure overload leads to cardiac hypertrophy, which is often followed by heart failure. We tested the hypothesis that depressed contractility in this process results from an imbalance in Ca 2+ transport by the sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) and the sarcolemmal Na+/Ca2+ exchanger (NCX).
  
  
  RESULTS
  Left ventricular (LV) myocytes (n = 79) from 12 normal (N) and 5 hypertrophied (LVH, by aortic banding) feline hearts were studied. Adenoviral gene transfer was used to introduce green fluorescent protein (GFP), SERCA2, and NCX into N and LVH myocytes. Contraction (videomicroscopy) and Ca2+ transients (Fluo-3) were measured in steady state and after rest periods of 2 to 120 seconds (rest decay and potentiation). LVH hearts were significantly larger than N (7.1 +/- 1.4 versus 4.2 +/- 0.2 g/kg). SERCA protein was significantly less abundant in LVH versus N. Steady state contractions and Ca2+ transients of LVH-GFP myocytes decayed more slowly and rest decay of contractility was more pronounced compared with N-GFP. Infection of LVH (and N) myocytes with SERCA increased basal contractility and reduced rest decay. Infection of LVH myocytes with NCX almost abolished contraction and in N myocytes reduced contractility and increased rest decay.
  
  
  CONCLUSIONS
  These findings suggest that an imbalance of Ca2+ transport by SERCA and the NCX produces the characteristic contractile abnormalities of hypertrophied cardiac myocytes.
authors.affiliation: Cardiovascular Research Group, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Jutta
authors.initials: J
authors.lastname: Weisser-Thomas
authors.forename: Hajime
authors.initials: H
authors.lastname: Kubo
authors.forename: Colleen A
authors.initials: CA
authors.lastname: Hefner
authors.forename: John P
authors.initials: JP
authors.lastname: Gaughan
authors.forename: Brian S
authors.initials: BS
authors.lastname: McGowan
authors.forename: Robert
authors.initials: R
authors.lastname: Ross
authors.forename: Markus
authors.initials: M
authors.lastname: Meyer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dillmann
authors.forename: Steven R
authors.initials: SR
authors.lastname: Houser
mesh_terms: D000818:Animals; D015153:Blotting, Western; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002415:Cats; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D006352:Heart Ventricles / Q000378:metabolism / Q000648:ultrastructure; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000502:physiology*; D008297:Male; D018715:Microscopy, Video; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D012508:Sarcolemma / Q000378:metabolism / Q000648:ultrastructure; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: D019831:Sodium-Calcium Exchanger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases