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, wh ich may contribute to their being at greater risk of developing drug-i nduced polymorphic ventricular arrhythmias. However, little is known a bout the underlying mechanisms. In the present study, we evaluated pot ential gender differences in Q-T interval in isolated perfused rabbit hearts using the Langendorff technique and evaluated the density of ou tward potassium currents in single ventricular myocytes using the whol e-cell patch-clamp technique. We found that female hearts demonstrated a greater Q-T lengthening (Delta Q-T%) upon an increase in cycle leng th (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 s howed a smaller I-ktail and peak I-Kl outward current density. A 50% r eduction 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 re lationship of I-Kr nor the gender difference in the Q-T-CL relationshi p was significantly altered. We conclude that 1) female rabbit ventric ular myocytes have significantly lower I-Kr and I-Kl outward current d ensities than do male cells, which may contribute to the gender differ ence in Q-T, and 2) a lower base-line I-Kr density may contribute to t he steeper Q-T-CL relationship in female hearts.