Background-Congestive heart failure (CHF) is frequently associated with atrial fibrillation (AF), but little is known about the effects of CHF on atrial cellular electrophysiology. Methods and Results-We studied action potential (AP) properties and ionic currents in atrial myocytes from dogs with CHF induced by ventricular pacing at 220 to 240 bpm for 5 weeks. Atrial myocytes from CHF dogs were hypertrophied (meanϮSEM capacitance, 89Ϯ2 pF versus 71Ϯ2 pF in control, nϭ160 cells per group, PϽ0.001). CHF significantly reduced the density of L-type Ca 2ϩ current (I Ca ) by Ϸ30%, of transient outward K ϩ current (I to ) by Ϸ50%, and of slow delayed rectifier current (I Ks ) by Ϸ30% without altering their voltage dependencies or kinetics. The inward rectifier, ultrarapid and rapid delayed rectifier, and T-type Ca 2ϩ currents were not altered by CHF. CHF increased transient inward Na ϩ /Ca 2ϩ exchanger (NCX) current by Ϸ45%. The AP duration of atrial myocytes was not altered by CHF at slow rates but was increased at faster rates, paralleling in vivo refractory changes. CHF created a substrate for AF, prolonging mean AF duration from 8Ϯ4 to 535Ϯ82 seconds (PϽ0.01). Conclusions-Experimental CHF selectively decreases atrial I to , I Ca , and I Ks , increases NCX current, and leaves other currents unchanged. The cellular electrophysiological remodeling caused by CHF is quite distinct from that caused by atrial tachycardia, highlighting important differences in the cellular milieu characterizing different clinically relevant AF

Abstract-The cardiac electrical system is designed to ensure the appropriate rate and timing of contraction in all regions of the heart, which are essential for effective cardiac function. Well-controlled cardiac electrical activity depends on specialized properties of various components of the system, including the sinoatrial node, atria, atrioventricular node, His-Purkinje system, and ventricles. Cardiac electrical specialization was first recognized in the mid 1800s, but over the past 15 years, an enormous amount has been learned about how specialization is achieved by differential expression of cardiac ion channels. More recently, many aspects of the molecular basis have been revealed. Although the field is potentially vast, an appreciation of key elements is essential for any clinician or researcher wishing to understand modern cardiac electrophysiology. This article reviews the major regionally determined features of cardiac electrical function, discusses underlying ionic bases, and summarizes present knowledge of ion channel subunit distribution in relation to functional specialization. Key Words: ion channels Ⅲ molecular biology Ⅲ conduction Ⅲ cardiac arrhythmias Ⅲ antiarrhythmic drugs C ardiac function depends on the appropriate timing of contraction in various regions, as well as on appropriate heart rate. To subserve these functions, electrical activity in each region is adapted to its specialized function. Regionally specialized cardiac electrical function was recognized in the mid 1800s, when Stannius 1 demonstrated that ligatures in the superior vena caval sinus region of the frog caused cardiac asystole, with the sinus continuing to beat. With the widespread application to cardiac ion channel study of patchclamp methodologies in the 1980s and molecular biology in the 1990s, many underlying mechanisms have been unraveled. The present article reviews the major regionally determined features of cardiac electrical function and the present knowledge regarding ionic and molecular bases. Overview of Regional Functional SpecificityFigure 1 illustrates typical regional action potential (AP) properties in the heart. The normal cardiac impulse originates in the sinoatrial node (SAN) and propagates through the atria to reach the atrioventricular node (AVN). From the AVN, electrical activity passes rapidly through the cable-like HisPurkinje system to reach the ventricles, triggering cardiac pumping action. Figure 2 shows the ionic currents involved in a schematic cardiac AP, provides standard abbreviations for currents and their corresponding subunits, and summarizes principal localization data discussed elsewhere in the present review. Ionic and Molecular Basis of Functional Specificity Sinoatrial Node Cellular Electrophysiology and FunctionThe SAN, located in the right atrial (RA) roof between the venae cavae, 2 is specialized for physiological pacemaker function. Heart rate control is achieved through autonomic regulation of SAN pacemaking. SAN APs have a relatively positive maximum diastolic potential (MDP...