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Vol. 285, Issue 2, 672-679, May 1998
Department of Pharmacology, Georgetown University Medical Center,
Washington, DC
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 (
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 IKtail and peak IKl outward
current density. A 50% reduction in extracellular K+ and
Mg++ shifted the I-V relationship of IKl 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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