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 (ΔQ-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 I_Ktail and peak I_Kl outward current density. A 50% reduction in extracellular K⁺ and Mg⁺⁺ shifted the I-V relationship of I_Kl and I_to and reduced their amplitude. However, neither the I-V relationship of I_Kr nor the gender difference in the Q-T–CL relationship was significantly altered. We conclude that 1) female rabbit ventricular myocytes have significantly lower I_Kr and I_Kl outward current densities than do male cells, which may contribute to the gender difference in Q-T, and 2) a lower base-line I_Kr density may contribute to the steeper Q-T–CL relationship in female hearts.