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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/H1895    most recent 00469.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wasserstrom, J. A. Articles by Aistrup, G. L. PubMed PubMed Citation Articles by Wasserstrom, J. A. Articles by Aistrup, G. L.

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

Departments of Medicine and of Molecular Pharmacology and Biological Chemistry and the Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois

Submitted 6 May 2008 ; accepted in final form 29 August 2008

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.

calcium transients; intercellular heterogeneity; confocal microscopy; T-wave alternans; calcium alternans; restitution