Gender difference in the cycle length-dependent QT and potassium currents in rabbits

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.