| Autor: |
Zhao, Wen, Frank, Konrad F., Chu, Guoxiang, Gerst, Michael J., Schmidt, Albrecht G., Ji, Yong, Periasamy, Muthu, Kranias, Evangelia G. |
| Předmět: |
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| Zdroj: |
Cardiovascular Research; Jan2003, Vol. 57 Issue 1, p71, 11p |
| Abstrakt: |
Objective: Phospholamban ablation or ectopic expression of SERCA1a in the heart results in significant increases in cardiac contractile parameters. The aim of the present study was to determine whether a combination of these two genetic manipulations may lead to further augmentation of cardiac function. Methods: Transgenic mice with cardiac specific overexpression of SERCA1a were mated with phospholamban deficient mice to generate a model with SERCA1a overexpression in the phospholamban null background (SERCA1OE/PLBKO). The cardiac phenotype was characterized using quantitative immunoblotting, sarcoplasmic reticulum calcium uptake and single myocyte mechanics and calcium kinetics. Results: Quantitative immunoblotting revealed an increase of 1.8-fold in total SERCA level, while SERCA2 was decreased to 50% of wild types. Isolated myocytes indicated increases in the maximal rates of contraction by 195 and 125%, the maximal rates of relaxation by 200 and 124%, while the time for 80% decay of the Ca2+-transient was decreased to 43 and 75%, in SERCA1OE/PLBKO hearts, compared to SERCA1a overexpressors and phospholamban knockouts, respectively. These mechanical alterations reflected parallel alterations in Vmax and EC50 for Ca2+ of the sarcoplasmic reticulum Ca2+ transport system. Furthermore, there were no significant cardiac histological or pathological alterations, and the myocyte contractile parameters remained enhanced, up to 12 months of age. Conclusions: These findings suggest that a combination of SERCA1a overexpression and phospholamban ablation results in further enhancement of myocyte contractility over each individual alteration. [Copyright &y& Elsevier] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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