Genetic background affects function and intracellular calcium regulation of mouse hearts.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Shah
Adarsh P
AP
Laboratory of Cell Electrophysiology, Heart Science Centre, National Heart and Lung Institute, Imperial College London, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK.
Siedlecka
Urszula
U
Gandhi
Ajay
A
Navaratnarajah
Manoraj
M
Al-Saud
Sara Abou
SA
Yacoub
Magdi H
MH
Terracciano
Cesare M
CM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size; D002940:Circadian Rhythm / Q000235:genetics; D004562:Electrocardiography; D056966:Excitation Contraction Coupling / Q000235:genetics*; D005838:Genotype; D006339:Heart Rate / Q000235:genetics; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009200:Myocardial Contraction / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D010641:Phenotype; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013045:Species Specificity; D013318:Stroke Volume / Q000235:genetics; D013686:Telemetry; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000235:genetics*
D002118:Calcium