Cited by 209Cardiac electrophysiology and arrhythmiasIon channel regulation and functionCardiac Arrhythmias and Treatments

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Gender Difference in the Cycle Length-Dependent QT and Potassium Currents in Rabbits

Liu, Xiao-Ke, Katchman, Alexander, Drici, Milou-Daniel, Ebert, Steven N., Ducic, Ivan, Morad, Martin, Woosley, Raymond L.·1998·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1016/s0022-3565(24)37435-x

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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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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)
ORCID: Drici, Milou-Daniel
Ebert, Steven N.
Morad, Martin
Woosley, Raymond L.
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)
DOI: 10.1016/s0022-3565(24)37435-x
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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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Gender Difference in the Cycle Length-Dependent QT and Potassium Currents in Rabbits

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