Characteristics of intracellular Ca2+ cycling in intact rat heart: a comparison of sex differences

Am J Physiol Heart Circ Physiol. 2008 Nov;295(5):H1895-904. doi: 10.1152/ajpheart.00469.2008. Epub 2008 Sep 5.


Males and females show distinct differences in action potential waveform, ion channel expression patterns, and ECG characteristics. However, it is not known how sex-based differences in Ca2+ cycling might contribute to these differences in electrophysiological activity. The goal of this study was to investigate the differences in cellular Ca2+ transients in males and females and to examine how these might contribute to electrophysiological function. Ca2+ transients were measured in individual myocytes within microscopic regions of the fluo-4 AM-loaded left ventricular epicardium of intact rat heart of both sexes (3 to 5 mo old). Pacing protocols were used to measure transient characteristics at a basic cycle length of 500 ms and during 10-s trains of rapid pacing delivered to the left ventricular apex. Ca2+ transients were smaller in magnitude and longer in duration in females than in males. More importantly, the variability in Ca2+ transient characteristics between myocytes in a microscopic recording site (heterogeneity index) was greater for females than males for characteristics related to transient duration. The rate sensitivity of Ca2+ alternans development in individual myocytes was greater in females than in males, but there was also a greater heterogeneity in cellular responses to the rate dependence of alternans development in females. The longer Ca2+ transients in females were also associated with slower restitution, which was likely to be responsible for the development of Ca2+ and repolarization alternans at slower heart rates. These results demonstrate that there are distinct differences in cellular Ca2+ cycling in male and female rat hearts. Not only is there slower reuptake of Ca2+ in female rats, but there is greater local variability in Ca2+ cycling at the microscopic level. These sex-based differences in Ca2+ cycling could contribute to differences in ECG morphology and in arrhythmia sensitivity in males and females.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials
  • Animals
  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / metabolism
  • Calcium Signaling*
  • Cardiac Pacing, Artificial
  • Female
  • Heart Ventricles / metabolism
  • In Vitro Techniques
  • Kinetics
  • Male
  • Microscopy, Confocal
  • Myocardium / metabolism*
  • Perfusion
  • Pericardium / metabolism
  • Rats
  • Sex Factors