title: Characteristics of intracellular Ca2+ cycling in intact rat heart: a comparison of sex differences.
abstract: 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.
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. ja-wasserstrom@northwestern.edu
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Wasserstrom
authors.forename: Sunil
authors.initials: S
authors.lastname: Kapur
authors.forename: Sabrina
authors.initials: S
authors.lastname: Jones
authors.forename: Tania
authors.initials: T
authors.lastname: Faruque
authors.forename: Rohan
authors.initials: R
authors.lastname: Sharma
authors.forename: James E
authors.initials: JE
authors.lastname: Kelly
authors.forename: Amanda
authors.initials: A
authors.lastname: Pappas
authors.forename: Wilson
authors.initials: W
authors.lastname: Ho
authors.forename: Alan H
authors.initials: AH
authors.lastname: Kadish
authors.forename: Gary L
authors.initials: GL
authors.lastname: Aistrup
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism; D020013:Calcium Signaling; D002304:Cardiac Pacing, Artificial; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D018613:Microscopy, Confocal; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010496:Pericardium / Q000378:metabolism; D051381:Rats; D012737:Sex Factors
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