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

J. Andrew Wasserstrom, Sunil Kapur, Sabrina Jones, Tania Faruque, Rohan Sharma, James E. Kelly, Amanda Pappas, Wilson Ho, Alan H. Kadish, Gary L. Aistrup

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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. Ca 2+ 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.

Original languageEnglish (US)
Pages (from-to)H1895-H1904
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number5
StatePublished - Nov 2008


  • Calcium alternans
  • Calcium transients
  • Confocal microscopy
  • Intercellular heterogeneity
  • Restitution
  • T-wave alternans

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology


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