Differences in Expression and Function in the Atrium versus Ventricle of the Sodium-Calcium Exchanger in the Embryonic Chicken Heart

Heart function is well known to be dependent on intrinsic electrical activity. This electrical activity is primarily mediated by a combination of interactions among various ionic channels and transporters. In this study, we demonstrate that the Na+-Ca2+ exchanger (NCX) is equally present in both atrial and ventricular cells at early stages of development (st. 13). However, ventricular cells exhibit an increase in NCX messenger ribonucleic acid (mRNA) levels during later stages of development, while levels in atrial cells remain constant. We demonstrate that the current density of the NCX increases with development in the ventricle but remains constant in the atrial cells. Furthermore we demonstrate that the NCX has a major role in shaping the cardiac action potential at early stages mainly in ventricular cells (st. 14) than later mainly in the atrial cells (st. 30). 1. Introduction The heart is one of the most important organs and its proper function is critical for normal complex organism development and survival. Its role during the development of the embryo has been widely studied for many years [1, 2]. The heart, in the simplest terms, is a tissue pump with the signal for its pumping action provided by spontaneous intrinsic electrical activity. The heart generates electrical activity throughout its lifetime and any irregularity in its generation and/or conduction can have lethal physiological implications [3, 4]. It is well recognized that the Na+-Ca2+ exchanger (NCX) is an integral component of the excitation-contraction coupling cycle in the adult cardiac muscle. The plasma membrane NCX is a bidirectional electrogenic (3Na+？:？1Ca2+) and voltage-sensitive ion transport mechanism, which is mainly responsible for the Ca2+ extrusion which follows excitation. For Ca2+ extrusion, energy is provided by the Na+ gradient which is established by the Na+ pump (for review see [5]). However, the NCX can also work in reverse mode. In this mode internal Na+ can be exchanged for external calcium. Thus, if the Na+-pump is inhibited, the elevated levels of Na+ inside the cell may increase the influx of Ca2+ via the NCX [5]. Cardiac contraction is initiated by influx of Ca2+ through voltage-dependent Ca2+ channels, which triggers a release of Ca2+ from the sarcoplasmic reticulum (SR) by a Ca2+-induced Ca2+ release mechanism. Relaxation is accomplished by the extrusion of Ca2+ from the cell by NCX and by re-uptake of Ca2+ into the SR (for review see [6, 7]). Thus, the NCX is the dominant cellular Ca2+ efflux mechanism in the myocardium in many species. Another