Genetic background affects function and intracellular calcium regulation of mouse hearts

Cardiovasc Res. 2010 Sep 1;87(4):683-93. doi: 10.1093/cvr/cvq111. Epub 2010 Apr 22.


Aims: The genetic background is currently under close scrutiny when determining cardiovascular disease progression and response to therapy. However, this factor is rarely considered in physiological studies, where it could influence the normal behaviour and adaptive responses of the heart. We aim to test the hypothesis that genetic strain variability is associated with differences in excitation-contraction coupling mechanisms, in particular those involved in cytoplasmic Ca(2+) regulation, and that they are concomitant to differences in whole-heart function and cell morphology.

Methods and results: We studied 8- to 10-week-old male C57BL/6, BALB/C, FVB, and SV129 mice. Echocardiography and radiotelemetry were used to assess cardiac function in vivo. FVB mice had increased left ventricular ejection fraction and fractional shortening with significantly faster heart rate (HR) and lack of diurnal variation of HR. Confocal microscopy, sarcomere length tracking, and epifluorescence were used to investigate cell volume, t-tubule density, contractility, and Ca(2+) handling in isolated ventricular myocytes. Sarcomere relaxation and time-to-peak of the Ca(2+) transient were prolonged in BALB/C myocytes, with more frequent Ca(2+) sparks and significantly higher sarcoplasmic reticulum (SR) Ca(2+) leak. There were no strain differences in the contribution of different Ca(2+) extrusion mechanisms. SV129 had reduced SR Ca(2+) leak with elevated SR Ca(2+) content and smaller cell volume and t-tubule density compared with myocytes from other strains.

Conclusion: These results demonstrate that a different genetic background is associated with physiological differences in cardiac function in vivo and differences in morphology, contractility, and Ca(2+) handling at the cellular level.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cell Size
  • Circadian Rhythm / genetics
  • Electrocardiography
  • Excitation Contraction Coupling / genetics*
  • Genotype
  • Heart Rate / genetics
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Myocardial Contraction / genetics
  • Myocardium / metabolism*
  • Phenotype
  • Sarcoplasmic Reticulum / metabolism
  • Species Specificity
  • Stroke Volume / genetics
  • Telemetry
  • Ultrasonography
  • Ventricular Function, Left / genetics*


  • Calcium