KB130015 [2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran] is an analogue of amiodarone, synthesized with the aim to keep beneficial but avoid side effects of the parent molecule. The drug was expected to have an action on various ion currents, especially a block of delayed rectifier currents as is the case with amiodarone. We have investigated the effect of KB130015 using the patch-clamp technique at 22°C on isolated membrane patches of Xenopus oocytes heterologously expressing hERG1, and the whole-cell voltage-clamp at 35°C on pig ventricular myocytes. In Xenopus oocyte membranes, 10 mM KB130015 had no effect when applied on the extracellular side of outside-out patches but markedly modified hERG1currents when applied on the intracellular side of inside-out patches. In patches expressing wild-type channels, the drug increased the amplitude and shortened the time-to-peak of the hERG1current elicited upon depolarization, and accelerated the rate of channel deactivation. In mutant S620T channels, which lack inactivation and were used to quantify the effect on activation, KB130015 accelerated the activation kinetics and shifted the steady-state voltage-dependent activation to more negative potentials. In contrast, amiodarone applied on the intracellular side of the patches only displayed a potent blocking effect. In cardiac cells exposed to extracellular KB130015, I_Kr was unchanged, whereas in cells dialyzed with 10 mM of the drug I_Kr deactivation tended to be faster. We conclude that KB130015 has novel effects on hERG1 channels, different from those of amiodarone. The drug may serve as a parent molecule for designing new compounds with stimulatory action on I_Kr, which could be useful for the treatment of hERG mutations that slow deactivation.