Wiring the developing heart: a serious matter for adulthood

Abstract

This editorial refers to ‘Exploration of human, rat and rabbit embryonic cardiomyocytes suggests K-channel block as a common teratogenic mechanism’ by C. Danielsson et al ., pp. 23–32, this issue. The normal functioning of the heart resides in its coordinated and effective pumping capacity. Contraction of the heart is provided by the ordered and intricate design of the contractile apparatus, the sarcomere, while the coordination of contraction is accomplished by the cardiac conduction system.1 At the cellular level, the electrical properties of the contracting cardiomyocytes are governed by a complex array of inward and outward ion currents that configure the cardiac action potential. If we take as a paradigm the human cardiomyocyte, upstroke sodium current ( I Na) is responsible for depolarization of the cardiomyocyte plasma membrane,2 whereas a variety of outward potassium currents ( I Kur, I Kr, I Ks, I K1, I TO) provide the means to repolarize the cell membrane as well as to keep constant the resting membrane potential.3,4 Electrical coupling—that is to say from conduction to contraction—is provided mainly by calcium currents ( I Ca).5 It is important to acknowledge the nature of the regulation of the cardiac action potential, since limited variability is observed within the sodium currents in atrial and ventricular cardiomyocytes, a situation that similarly applies to the electrical coupling governed by calcium currents. However, a large variability is observed for the repolarization and resting membrane potential.6,7 For example, distinct resting membrane potential and cardiac action potential morphologies are observed for atrial and ventricular myocytes, and even within ventricular …