MCC-134, a Novel Vascular Relaxing Agent, Is an Inverse Agonist for the Pancreatic-Type ATP-Sensitive K1 Channel1

The effects of a novel vasorelaxant agent, MCC-134 (1-[4-(1H-imidazol-1-yl)benzoyl]-N-methyl-cyclobutanecarbothioamide), were examined on reconstituted ATP-sensitive K1 (KATP) chan-nels, which are composed of an inwardly rectifying K1 channel, Kir6.2, and three types of sulfonylurea receptors (SUR): SUR1, SUR2A, and SUR2B. Each type of KATP channel was heterolo-gously expressed in human embryonic kidney 293T cells. The expressed KATP channel currents were measured with the whole-cell configuration of the patch-clamp method. MCC-134 activated the SUR2B/Kir6.2 channel, was a weak activator of the SUR2A/Kir6.2 channel, but did not activate the SUR1/Kir6.2 channel. MCC-134 suppressed SUR1/Kir6.2 channel currents that had been fully activated by either diazoxide or NaCN, whereas it did not affect the fully activated SUR2A/Kir6.2 o