Atrial fibrillation (AF) is associated with increased morbidity and is in 
addition the most prevalent cardiac arrhythmia. Compounds used in 
pharmacological treatment has traditionally been divided into Na(+) channel 
inhibitors, β-blockers, K(+) channel inhibitors, and Ca(2+) channel inhibitors, 
whereas newer multichannel blockers such as amiodarone and ranolazine have been 
introduced later. This study was devoted to the evaluation of an acute 
pacing-induced in vivo model of AF in rats. Antiarrhythmic effects of well-known 
compounds such as lidocaine, dofetilide, and ranolazine were confirmed in this 
model. In addition, antiarrhythmic effects of different inhibitors of 
Ca(2+)-activated small conductance K(+) (SK) channels were demonstrated. 
Intravenous application of 5 mg/kg of the negative SK channel modulator NS8593 
reduced AF duration by 64.5%, and the lowest significantly effective dose was 
1.5 mg/kg. A dose-effect relationship was established based on 6 different dose 
groups. Furthermore, it was demonstrated that the antiarrhythmic effect of 
NS8593 and other tested drugs was associated with an increase in atrial 
effective refractory period. The functional role of SK channels was confirmed by 
2 other SK channel inhibitors, UCL1684 and apamin, thereby confirming the 
hypothesis that these channels might constitute a new promising target for 
antiarrhythmic treatment.