Intravenous application of 5 mg/kg of the SK channel modulator NS8593 reduced pacing-induced atrial fibrillation duration by 64.5% in an in vivo rat model.
Does inhibition of small conductance Ca2+-activated K+ channels reduce the duration of pacing-induced atrial fibrillation in rats?
Inhibition of small conductance Ca2+-activated K+ channels reduces the duration of pacing-induced atrial fibrillation in rats, suggesting a potential new target for antiarrhythmic treatment.
Effect estimate: 64.5% reduction
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.
Skibsbye et al. (Thu,) conducted a other in Atrial fibrillation. NS8593 (SK channel inhibitor) was evaluated on Atrial fibrillation duration (64.5% reduction). Intravenous application of 5 mg/kg of the SK channel modulator NS8593 reduced pacing-induced atrial fibrillation duration by 64.5% in an in vivo rat model.