Gender differences in cardiac electrophysiology

Gender differences in electrocardiographic (ECG) variables and incidence of cardiac arrhythmias exist. Females have longer rate-corrected QT (QTc) intervals and are more susceptible than males to arrhythmias caused by QT prolongation. These observations indicate that fundamental gender differences in electrophysiologic properties exist. Previous experimental studies have provided supportive evidence for this concept, as they have shown gender disparity in the expression and density of some of the major sarcolemmal ion currents that control cardiac excitability, i.e., transient outward K⁺ current (I_to), rapid delayed rectifier K⁺ current (I_Kr), and L-type Ca²⁺ current (I_Ca,L). In the present study, we evaluated the role of gender-related differences in I_to, I_Kr, and I_Ca,L densities on cellular cardiac (patho)electrophysiology. We modified ion current amplitudes in the Priebe and Beuckelmann (PB) human ventricular model cell according to experimental data obtained from male and female hearts, and studied action potentials and the susceptibility to arrhythmias. We found that the "female" model cell has longer action potentials, a higher "notch\´ level, a steeper action potential duration (APD) vs. frequency relationship, and an enhanced susceptibility to early afterdepolarizations. These findings may explain the clinical findings of gender differences in cardiac (patho)electrophysiology.