Atrial fibrillation involves cumulative electrophysiological remodeling, including reductions in L-type Ca2+ and K+ currents, and oxidative injury that may contribute to its pathophysiology.
This review highlights the specific cellular electrophysiological alterations and oxidative stress mechanisms underlying atrial remodeling in atrial fibrillation, providing potential targets for future pharmacological therapies.
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 Ca2+ current, ICa,L, the transient outward K+ current, ITO, and the ultra-rapid delayed rectifier K+ current, IKur, in atrial myocytes from patients in persistent or permanent AF. The density of the muscarinic K+ current (IKACh) is also reduced, however the inward rectifier K+ current (IK1) 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 ICa,L 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.
David R. Van Wagoner (Mon,) conducted a review in Atrial fibrillation. Atrial fibrillation involves cumulative electrophysiological remodeling, including reductions in L-type Ca2+ and K+ currents, and oxidative injury that may contribute to its pathophysiology.