KR-30450, a newly synthesized benzopyran derivative, activates the cardiac ATP-sensitive K⁺ channel

KR-30450 (2-(2''(1'',3''-dioxolone)-2-methyl-4-(2'-oxo-1'-pyrrollidinyl)- 6-nitro-2H-1-benzopyren) is a newly synthesized benzopyran derivative. We examined the effect of KR-30450 on the action potential duration of isolated rat papillary muscle and on the ATP-sensitive K⁺ channel (K(ATP)) activity in single rat ventricular myocytes with 3 M KCl-filled conventional microelectrode and patch clamp techniques. KR-30450 (10^-7 ~ 10^-5 M) reduced the action potential duration in a concentration-dependent manner and this was inhibited by 3 μM glibenclamide, suggesting that K(ATP) was involved. In cell-attached patches, KR-30450 (10^-5 M) in the pipette activated the K(ATP), which was closed by 3 μM glibenclamide. In inside-out patches, the effects of KR-30450 on K(ATP) activity were examined before and after run-down of the channel. Before run-down, KR-30450 increased the K(ATP) activity only in the presence of ATP and shifted the [ATP](i) - K(ATP) activity relationship to the right. After run-down, KR-30450 did not affect the K(ATP) activity either in the presence or absence of 3 mM UDP, but increased the UDP-induced K(ATP) activity in the presence of 1 mM ATP-γ-S. From these results, we conclude that KR-30450 antagonizes the inhibitory effect of ATP on the K(ATP) in a competitive manner. These effects of KR- 30450 are similar to those of ER-001533 and HOE-234, but different from those of pinacidil and lemakalim.