Sex differences exist in the cardiac electrophysiology between men and women. Women are more susceptible to arrhythmias related to prolonged QT interval (i.e., to decelerated final repolarization due to reduced repolarization reserve), whereas men show arrhythmias related to all-or-none repolarization more often, observed, e.g., in Brugada syndrome (due to accelerated early repolarization and reduced depolarization reserve). Underlying sex-specific features of cardiac cellular electrophysiology (action potential [AP] and basic ionic membrane currents) have been partly revealed, as is reviewed in detail in this chapter. Briefly, the deceleration of cardiac repolarization (i.e., the longer duration of AP) in adult women is mostly resulting from an increase of depolarizing L-type calcium current and a decrease of various repolarizing potassium currents, both caused by estrogen action (both genomic and nongenomic). Mathematical cell and tissue simulations suggested formation of early afterdepolarizations and reentry during late follicular phase (when the estrogen levels are high) in the presence of consequent drug-induced deceleration of cardiac repolarization. Testosterone and progesterone show opposite effects in the majority of ionic currents (again both genomic and nongenomic), thus accelerating the cardiac repolarization that protects the cardiac tissue against arrhythmias related to prolonged QT interval. Knowledge about sex-related differences in cardiac electrophysiology should be further improved, for example, to enable more reliable sex-specific treatment of arrhythmias and safety pharmacology testing.
Sex and Cardiac Electrophysiology, Academic Press, 2020, Pages 201-210,