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American journal of physiology. Heart and circulatory physiology, 2000-06, Vol.278 (6), p.H1924-H1932
2000

Details

Autor(en) / Beteiligte
Titel
SERCA2a activity correlates with the force-frequency relationship in human myocardium
Ist Teil von
  • American journal of physiology. Heart and circulatory physiology, 2000-06, Vol.278 (6), p.H1924-H1932
Ort / Verlag
United States
Erscheinungsjahr
2000
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
  • 1  Laboratory of Muscle Research and Molecular Cardiology, Klinik III für Innere Medizin; 2  Department of Cardiac and Thoracic Surgery; and 3  Department of Anatomy, Universität zu Köln, 50924 Cologne, Germany The present investigation addresses whether protein expression and function of sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA2a) and phospholamban (PLB) correlate in failing and nonfailing human myocardium. SERCA2a activity and protein expression, PLB phosphorylation, and the force-frequency relationship (FFR) have been determined in right atrium (RA) and left ventricle (LV) from nonfailing (NF, n  = 12) and terminally failing [dilated cardiomyopathy (DCM), n  = 12] human hearts. Only in LV of DCM hearts was SERCA2a activity significantly decreased [maximal turnover rate ( V max ) = 196 ± 11 and 396 ± 30 nmol · mg 1 · min 1 in LV and RA, respectively], whereas protein expression of SERCA2a in the different chambers was unchanged in NF (3.9 ± 0.3 and 3.2   ± 0.4 densitometric units in LV and RA, respectively) and DCM hearts (4.8 ± 0.8 and 3.4 ± 0.1 densitometric units in LV and RA, respectively). Phosphorylation of PLB was higher in LV than in RA in NF (Ser 16 : 180.5 ± 19.0 vs. 56.8 ± 6.0 densitometric units; Thr 17 : 174.6 ± 11.2 vs. 37.4 ± 8.9 densitometric units) and DCM hearts (Ser 16 : 132.0 ± 5.4 vs. 22.4 ± 3.5 densitometric units; Thr 17 : 131.2 ± 10.9 vs. 9.2 ± 2.4 densitometric units). SERCA2a function, but not protein expression, correlated well with the functional parameters of the FFR in DCM and NF human hearts. Regulation of SERCA2a function depends on the phosphorylation of PLB at Ser 16 and Thr 17 . However, direct SERCA2a regulation might also be affected by an unknown mechanism. heart failure; phospholamban phosphorylation; sarco(endo) plasmic reticulum calcium-adenosine 5'-triphosphatase

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