| First Author | Zhao W | Year | 2003 |
| Journal | Cardiovasc Res | Volume | 57 |
| Issue | 1 | Pages | 71-81 |
| PubMed ID | 12504816 | Mgi Jnum | J:102590 |
| Mgi Id | MGI:3607812 | Doi | 10.1016/s0008-6363(02)00609-0 |
| Citation | Zhao W, et al. (2003) Combined phospholamban ablation and SERCA1a overexpression result in a new hyperdynamic cardiac state. Cardiovasc Res 57(1):71-81 |
| abstractText | 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. |
