Electrical remodeling in atrial fibrillation - cellular and molecular mechanisms

Atrial fibrillation is associated with changes in atrial electrophysiology that facilitate the initiation and persistence of the arrhythmia. The under lying cellular and molecular mechanisms are diverse; they have intensively been investigated over the past few years. The results, that have substanti ally improved the understanding of the pathophysiology of atrial fibrillati on are reviewed. On the cellular level, atrial fibrillation leads to a stro ng shortening and an impaired rate adaptation of the action potential as we ll as changes in action potential morphology. Atrial fibrillation is associ ated with an altered gene expression of the L-type calcium channel (I-Ca,I- L) and of potassium channels (I-to, I-Kl, I-KACh). The molecular mechanisms of intraatrial conduction slowing are less well understood; changes in the expression or distribution of gap junction proteins or a decrease of the f ast sodium inward channel (I-Na) Seem to be involved. A trigger for many of the observations is an overload of the myocyte cytoplasm with Ca2+ and a c onsecutive decrease of the systolic calcium gradient, furthermore changes i n calcium-handling proteins are detectable in atrial fibrillation. In the l ast part, the clinical relevance and potential new therapeutic approaches a re discussed.