Key Points
- To determine the contractile and calcium-handling changes produced by cardiac overexpression of the sarcoplasmic reticulum Ca2+ ATPase (SERCA2) in transgenic mice.
- Generated transgenic mouse lines (heterozygous CJ5 and homozygous CJ2) overexpressing the rat SERCA2 transgene in cardiac tissue.
- Quantified SERCA2 mRNA, protein abundance, and synthesis rate alongside other calcium-handling genes including phospholamban and calsequestrin.
- Evaluated contractile mechanics and calcium transients in isolated ventricular myocytes, papillary muscles, and in vivo under basal conditions and isoproterenol stimulation.
- Heterozygous CJ5 mice displayed a 2.6-fold increase in SERCA2 mRNA, a 1.2-fold increase in SERCA2 protein, and an 82% increase in protein synthesis rate relative to controls.
- Isolated cardiac myocytes exhibited a 23% faster half-time (t1/2) of intracellular calcium decline and a 22% faster half-time of relengthening, with significantly accelerated shortening rates.
- In vivo cardiac hemodynamic measurements and papillary muscle assays demonstrated significantly accelerated contraction and relaxation velocities at baseline and during isoproterenol treatment.
Structured PICO
Does overexpression of the SERCA2 gene improve calcium transients and cardiac relaxation in transgenic mice?
PPopulationTransgenic mice overexpressing a rat SERCA2 transgene (heterozygous line CJ5 and homozygous line CJ2)
IInterventionOverexpression of rat SERCA2 gene
CComparatorNegative littermates (control mice)
OOutcomeCalcium handling and contractile parameters (intracellular calcium decline, myocyte relengthening, rate of myocyte shortening, in vivo cardiac function)surrogate
In vivo overexpression of SERCA2 enhances calcium transients, myocardial contractility, and relaxation in transgenic mice, highlighting a potential therapeutic target for heart failure.