Gender Difference in the Cycle Length-Dependent QT and Potassium Currents in Rabbits
Abstract
Women are known to have a longer electrocardiographic Q-T than men, which may contribute to their being at greater risk of developing drug-induced polymorphic ventricular arrhythmias. However, little is known about the underlying mechanisms. In the present study, we evaluated potential gender differences in Q-T interval in isolated perfused rabbit hearts using the Langendorff technique and evaluated the density of outward potassium currents in single ventricular myocytes using the whole-cell patch-clamp technique. We found that female hearts demonstrated a greater Q-T lengthening (delta Q-T%) upon an increase in cycle length (CL), resulting in a significantly longer Q-T (301 +/- 4.8 ms, CL = 2.3 s) at a long CL in female hearts compared with male hearts (267 +/- 4.0 ms, P < .01). Ventricular myocytes isolated from female hearts showed a smaller IK(tail) and peak IKI outward current density. A 50% reduction in extracellular K+ and Mg++ shifted the I-V relationship of IKI and Ito and reduced their amplitude. However, neither the I-V relationship of IKr nor the gender difference in the Q-T-CL relationship was significantly altered. We conclude that 1) female rabbit ventricular myocytes have significantly lower IKr and IKl outward current densities than do male cells, which may contribute to the gender difference in Q-T, and 2) a lower base-line IKr density may contribute to the steeper Q-T-CL relationship in female hearts.
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The bulk of studies evaluating sex differences in the AF-related risk of heart failure have showed no significant difference; however, a few studies have suggested higher risk in women.
“The bulk of studies evaluating sex differences in the AF-related risk of HF have showed no significant difference; however, a few studies have suggested higher risk in women (Supplementary Table S8).”
From Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis (2016) · cites this paper as [97]
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- Authors
- Liu, X.-K., Katchman, A., Drici, M.-D., Ebert, S. N., Ducic, I., Morad, M., & Woosley, R. L.
- Affiliations
- Georgetown University Medical Center (US)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1998-05
- Volume
- 285
- Issue
- 2
- Pages
- 672-679
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2210759123
- Cited by
- 209
- References
- 29
- Citations by year
- 2026: 3 · 2025: 3 · 2023: 3 · 2022: 6 · 2021: 4 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 9 · 2014: 4 · 2013: 13 · 2012: 7
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Institutes of Health (5r01hl054590-05)
- National Heart, Lung, and Blood Institute (R01 HL54590)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Keywords
- gender differences, QT interval, cycle length, outward potassium current, IKr, inward rectifier potassium current, ventricular myocytes, ventricular repolarization, extracellular potassium, extracellular magnesium, drug-induced ventricular arrhythmia, rabbit heart
- MeSH terms
- Animals, Electrocardiography, Female, Magnesium, Male, Potassium, Rabbits, Sex Factors, Potassium Channels
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