Atrial fibrillation (AF) is presently the most common cardiac arrhythmia in clinical practice. Its treatment is The identification of the molecular structure of many ion inadequate. Maintenance of normal sinus rhythm (SR) is channels involved in cardiac excitability and their funcobviously the optimal approach, but is difficult to achieve tional correlation with native ionic currents have made it without drugs that have the potential to cause ventricular possible to study the effects of pathophysiological conproarrhythmia and increase mortality. Non-pharmacologi- ditions, like AF, at different levels from genes to ionic cal therapy is attractive, but to date has not reached the currents. The different steps underlying the expression of same level of efficacy as in the treatment of arrhythmias an ion channel are depicted in Fig. 1 and have recently other than AF. In order to improve therapeutic approaches, been reviewed by Roden and Kupershmidt [1]. A DNA it is important to understand the detailed pathophysiology sequence containing the genetic code for an ion channel of the arrhythmia. A key component to the pathophysiol- subunit is transcribed into a pre-mRNA in the nucleus. ogy of any cardiac arrhythmia is the cellular milieu in This pre-mRNA is modified in different manners. The which it occurs. Changes in ion transport processes, non-coding (intronic) sequences are excised, a process including pumps, channels and exchangers, are central to termed RNA splicing. Different splice variants have been alterations in action potential properties that govern the described for several ion channels, including Kv4. 3 (the occurrence of arrhythmias like AF. Action potential dura- pore-forming (α) subunit of the transient outward current, tion (APD) determines the refractory period and is there- I), KvLQT1 (the α-subunit of the slow delayed-rectifier to fore a key determinant of the likelihood of reentry. I) and HERG (the α-subunit of the rapid delayed-