Fig. 5. Overlapping drug binding sites of high and low affinity TASK-1 inhibitors. As previously reported, Vaughan Williams class I (propafenone), II (carvedilol) and III (amiodarone) antiarrhythmic drugs display strong TASK-1 inhibition when applied in supratherapeutic levels (100 µM). In TASK-1 channels harboring a L239A/N240A double mutation effects of propafenone (a), carvedilol (b) and amiodarone (c) are virtually abolished. Data are presented as mean plus minus S.E.M.. * p<0.05, ** p<0.01, *** p<0.001.