Electrophysiological Remodeling in Human Atrial Fibrillation

<jats:p> <jats:italic>Atrial fibrillation (AF) is a progressive disease characterized by cumulative electrophysiological and structural remodeling of the atria. Cellular electrophysiological studies have revealed marked reductions in the densities of the L‐type voltage‐gated Ca<jats:sup>2+</jats:sup> current, I<jats:sub>Ca,L,</jats:sub> the transient outward K<jats:sup>+</jats:sup> current, I<jats:sub>TO</jats:sub>, and the ultra‐rapid delayed rectifier K<jats:sup>+</jats:sup> current, I<jats:sub>Kur</jats:sub>, in atrial myocytes from patients in persistent or permanent AF. The density of the muscarinic K<jats:sup>+</jats:sup> current (I<jats:sub>KACh</jats:sub>) is also reduced, however the inward rectifier K<jats:sup>+</jats:sup> current (I<jats:sub>K1</jats:sub>) density is increased. The net shortening or lengthening of the action potential is dependent on the balance between changes in inward and outward currents. The prominent reduction in I<jats:sub>Ca,L</jats:sub> appears to be sufficient to explain the observed decreases in action potential duration and effective refractory period that are characteristic of the fibrillating atria. Earlier studies have shown that calcium overload and perturbations in calcium handling play prominent roles in AF induced atrial remodeling. More recently, we have shown that AF is associated with evidence of oxidative injury to atrial tissue, and suggested that oxidative stress may directly contribute to the pathophysiology of AF. It is anticipated that insights gleaned from mechanistic studies will facilitate the development of improved pharmacological approaches to treat AF and to prevent the progression of arrhythmia. (PACE 2003; 26[Pt. II]:1572–1575)</jats:italic> </jats:p>