Cellular electrophysiology of atrial fibrillation.

Time for primary review 23 days. Atrial fibrillation (AF) is presently the most common cardiac arrhythmia in clinical practice. Its treatment is inadequate. Maintenance of normal sinus rhythm (SR) is obviously the optimal approach, but is difficult to achieve without drugs that have the potential to cause ventricular proarrhythmia and increase mortality. Non-pharmacological therapy is attractive, but to date has not reached the same level of efficacy as in the treatment of arrhythmias other than AF. In order to improve therapeutic approaches, it is important to understand the detailed pathophysiology of the arrhythmia. A key component to the pathophysiology of any cardiac arrhythmia is the cellular milieu in which it occurs. Changes in ion transport processes, including pumps, channels and exchangers, are central to alterations in action potential properties that govern the occurrence of arrhythmias like AF. Action potential duration (APD) determines the refractory period and is therefore a key determinant of the likelihood of reentry. Maximum Na+-current ( I Na) governs phase 0 upstroke velocity, determining conduction velocity (CV) and contributing to the likelihood of reentry. Delayed and early afterdepolarizations produce abnormal activity that can in themselves produce tachyarrhythmias and can trigger reentrant arrhythmia. This paper reviews these aspects of the cellular electrophysiology of AF, attempting to summarize what is known, what remains to be explored and what this information can teach us about why AF occurs and how to treat it. The identification of the molecular structure of many ion channels involved in cardiac excitability and their functional correlation with native ionic currents have made it possible to study the effects of pathophysiological conditions, like AF, at different levels from genes to ionic currents. The different steps underlying the expression of an ion channel are depicted in Fig. 1 and have recently been reviewed by Roden and … * Corresponding author. Tel.: +49-7071-298-3196; fax: +49-7071-294-121 ralph.bosch{at}uni-tuebingen.de