Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Zhao, W; Frank, KF; Chu, G; Gerst, MJ; Schmidt, AG; Ji, Y; Periasamy, M; Kranias, EG.
Combined phospholamban ablation and SERCA1a overexpression result in a new hyperdynamic cardiac state.
Cardiovasc Res. 2003; 57(1): 71-81.
Doi: 10.1016/S0008-6363(02)00609-0
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- Co-Autor*innen der Med Uni Graz
- Schmidt Albrecht
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- Abstract:
- 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 (SERCA1(OE)/PLB(KO)). 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 Ca(2+)-transient was decreased to 43 and 75%, in SERCA1(OE)/PLB(KO) hearts, compared to SERCA1a overexpressors and phospholamban knockouts, respectively. These mechanical alterations reflected parallel alterations in V(max) and EC(50) for Ca(2+) of the sarcoplasmic reticulum Ca(2+) 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Calcium - metabolism
- Calcium-Binding Proteins - genetics
- Calcium-Transporting ATPases - analysis Calcium-Transporting ATPases - genetics
- Cell Size -
- Gene Deletion -
- Gene Expression -
- Immunoblotting -
- Mice -
- Mice, Knockout -
- Mice, Transgenic -
- Myocardial Contraction -
- Myocardium - metabolism
- Sarcoplasmic Reticulum - metabolism
- Sarcoplasmic Reticulum Calcium-Transporting ATPases -
- Find related publications in this database (Keywords)
- Ca-pump
- contractile function
- myocytes
- SR (function)