Gender disparities in cardiac cellular electrophysiology and arrhythmia susceptibility in human failing ventricular myocytes

Gender disparities in ECG variables and susceptibility to arrhythmia exist. The basis of these sex-related distinctions in cardiac electrophysiology has been extensively Studied ill Various species, but is virtually unexplored ill humans. The aim of this Study was to clarify the cellular basis of electrophysiological gender disparities ill human cardiac myocytes. Human midmyocardial left ventricular myocytes were isolated from explanted hearts of male and female patients in end-stage heart failure at the time of cardiac transplantation. The action potentials, sarcolemmal ion currents, and Susceptibility to the generation of early afterdepolarizations were studied using whole-cell patch-clamp methodology. The functional effects of gender disparities in sarcolemmal ion Currents were assessed by computer simulations using the Priebe-Beuckelmann or the tell Tusscher-Noble-Noble-Panfilov human ventricular cell models. Female myocytes had significantly longer action potentials and greater Susceptibility to early afterdepolarizations than male myocytes. All other action potential parameters (resting membrane potential, amplitude, plateau level, upstroke velocity, maximal velocity of phase-1 and phase-3 repolarization) had similar values for both genders. In female myocytes, the transient outward potassium current (I-tot) tended to be smaller, while the L-type calcium current (I-Ca,I-L) and quasi-steady state Current (I-QSS) tended to be larger. Computer simulations showed that these Subtle differences in sarcolemmal ion Currents may conspire to cause the observed gender disparities ill action potential properties. Female failing myocytes have longer action potentials and a greater Susceptibility to early afterdepolarizations than male failing myocytes. These gender disparities may be due to slightly larger depolarizing I-Ca,I-L in conjunction with slightly smaller repolarizing I-QSS and I-tol in female myocytes.