β-3 adrenoceptor (AR) counteracts the β-1 and β-2 ARs and rescues the effects of excessive catecholamines. To test the hypothesis that a β-3 AR agonist (mirabegron) can reverse the effects of isoproterenol (ISO) on ventricular fibrillation (VF), we performed optical mapping studies in six male and six female Langendorff perfused rabbit hearts at baseline and after sequential administration of ISO (100 nm), mirabegron (1000 nm), apamin (100 nm) and washout (Study I). An additional six male and six female hearts were studied with mirabegron doses ranging between 250 and 1000 nm without ISO (Study II). Patch clamp studies in human embryonic kidney 293 cells were performed to determine the effect of mirabegron on the apamin-sensitive small conductance Ca