Cardiac conduction system

Ever since the first description of sex-related electrocardiographic differences was made by Bazett (1920), a substantial number of animal and human studies exploring the underlying mechanisms have revealed their multifactorial genesis. Women have a faster heart rate, shorter conduction times through the atria and the atrioventricular node, and a longer ventricular repolarization time than men. Different expression of ion-channel subunits, connexins (Cxs), and Ca2+-handling proteins provide a molecular basis for sex-related differences in the cardiac conduction system (CCS). Women are found to have weaker repolarizing currents due to a lower expression of a variety of K+-channel subunits in the ventricles compared with men. The initial appearance of some sex-related differences at puberty and their decline with age suggest an important role of sex hormones and autonomic influences on conduction properties. The effects of sex steroid hormones are mediated via both genomic and nongenomic signaling pathways. Estrogen is shown to shorten the atrial action potential duration (APD) and to prolong the ventricular APD. Testosterone, on the contrary, shortens the ventricular APD. Further research is needed to explain the full complexity of the underlying mechanisms of sex-related differences.