{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:30:01Z","timestamp":1789194601124,"version":"build-2803163510"},"reference-count":24,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:p> 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 Ca<jats:sup>2+<\/jats:sup> cycling might contribute to these differences in electrophysiological activity. The goal of this study was to investigate the differences in cellular Ca<jats:sup>2+<\/jats:sup> transients in males and females and to examine how these might contribute to electrophysiological function. Ca<jats:sup>2+<\/jats:sup> 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<jats:sup>2+<\/jats:sup> transients were smaller in magnitude and longer in duration in females than in males. More importantly, the variability in Ca<jats:sup>2+<\/jats:sup> 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 Ca<jats:sup>2+<\/jats:sup> 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 Ca<jats:sup>2+<\/jats:sup> transients in females were also associated with slower restitution, which was likely to be responsible for the development of Ca<jats:sup>2+<\/jats:sup> and repolarization alternans at slower heart rates. These results demonstrate that there are distinct differences in cellular Ca<jats:sup>2+<\/jats:sup> cycling in male and female rat hearts. Not only is there slower reuptake of Ca<jats:sup>2+<\/jats:sup> in female rats, but there is greater local variability in Ca<jats:sup>2+<\/jats:sup> cycling at the microscopic level. These sex-based differences in Ca<jats:sup>2+<\/jats:sup> cycling could contribute to differences in ECG morphology and in arrhythmia sensitivity in males and females. <\/jats:p>","DOI":"10.1152\/ajpheart.00469.2008","type":"journal-article","created":{"date-parts":[[2008,9,5]],"date-time":"2008-09-05T21:24:27Z","timestamp":1220649867000},"page":"H1895-H1904","source":"Crossref","is-referenced-by-count":42,"title":["Characteristics of intracellular Ca<sup>2+<\/sup> cycling in intact rat heart: a comparison of sex differences"],"prefix":"10.1152","volume":"295","author":[{"given":"J. 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