KB130015 [2-methyl-3-(3,5-diiodo-4-carboxymethoxy benzyl) benzofuran] (KB) was developed as novel class III antiarrhythmic drug with improved bioavailability and clearance compared to its parent molecule amiodarone (Mubagwa et al., 2003, Cardiovasc Drug Rev 21:216–235). Here we investigated the influence of KB on porcine pulmonary artery rings. After precontraction with prostaglandin F2a, 25–100 mM KB relaxed the rings. This effect was maintained in the presence of L-NAME, an inhibitor of endothelium-dependent relaxation, and inhibited with either 1 mM TEA or 1 mM paxilline, a specific blocker of Ca ²⁺-activated K⁺ (BK_Ca) channels. hSlo1, the principal a-subunit of BK_Ca channels, was expressed in HEK293 cells. In inside-out patches with 3 mM free cytosolic Ca ²⁺, 100 mM KB shifted the half-maximal activation voltage from 47±7 to -6±6 mV (n=6). This shift was concentration dependent with an EC₅₀ of 21 mM and a Hill coefficient of 2.6. BK_Ca activation was also observed in the absence of intracellular Ca²⁺. Coexpression of the auxiliary b-subunit hSlo b1 even enhanced the KB-mediated activation of the BK_Ca channel complex. We conclude that the vasorelaxing effect of KB results from Ca²⁺-independent activation of BK_Ca channels in vascular smooth muscle cells. The amiodarone derivative KB130015 therefore is a potent BK_Ca channel opener.