title: Transgenic overexpression of heart-specific adenine nucleotide translocase 1 positively affects contractile function in cardiomyocytes.
abstract: OBJECTIVE
  The adenine nucleotide translocase (ANT) exchanges ATP and ADP over the inner mitochondrial membrane, supplying the cells with energy. Interestingly, myocardial ANT1 overexpression preserves cardiac structure and function under pathophysiological conditions. To ascertain whether the contractile system is directly affected by increased ANT1 expression, we analyzed cell morphology, contraction and relaxation parameters of ANT1 transgenic (ANT1-TG) cardiomyocytes, myofibrillar protein expression, and Ca(2+) handling in ANT1-TG rat hearts.
  
  
  RESULTS
  ANT1-TG cardiomyoycytes displayed an elevation in cell volume (52.6 ± 12.0%; p<0.0001) in comparison to wildtype (WT) cells. Concurrently, contractile function in ANT1-TG cells was significantly increased, measured by a decline in time to peak contraction (TTP) and RT50, the time from peak contraction to 50% relaxation, during stimulation with 0.5, 1, and 2 Hz. Quantification of myofibrillar proteins exhibited a marked increase in total cardiac myosin heavy chain (51.8 ± 12.8%) (p<0.03), beta myosin heavy chain (22.9 ± 5.0%; p<0.03), actin (23.8 ± 8.8%; p<0.05), and troponin I (51.5 ± 13.7%; p<0.01). Regarding intracellular Ca(2+) handling, ANT1-TGs revealed a significant elevation in sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA2a) protein level (22.2 ± 4.7%; p<0.01) associated with increased Ca(2+) uptake into the SR (34%; p<0.01). Moreover, the plasmalemmal Ca(2+) ATPase (PMCA) indicated advanced protein expression (23.8 ± 4.8%; p<0.01), whereas the protein amount of the Na(+)/Ca(2+) exchanger was not altered in ANT1 overexpressing hearts.
  
  
  CONCLUSIONS
  These data reveal a close association of elevated mitochondrial ATP/ADP transportation via ANT1 with increased contractile function. Furthermore, the ANT1-TGs exhibit an elevation in SR Ca(2+) transport that contributes to increased cardiac work, which may protect the heart under pathophysiological conditions.
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Vogelpohl
authors.forename: Roland
authors.initials: R
authors.lastname: Vetter
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Heger
authors.forename: Linda
authors.initials: L
authors.lastname: Ebermann
authors.forename: Gerhild
authors.initials: G
authors.lastname: Euler
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Andrea
authors.initials: A
authors.lastname: Dörner
mesh_terms: D000199:Actins / Q000378:metabolism; D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D002478:Cells, Cultured; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D009218:Myosins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism
chemical_list: D000199:Actins; D033741:Adenine Nucleotide Translocator 1; D019210:Troponin I; D000255:Adenosine Triphosphate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D009218:Myosins; D002118:Calcium