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

YG Kwak, SK Park, HS Kang, JS Kim, SW Chae, KP Cho, SE Yoo and D Kim

Department of Pharmacology, Chonbuk National University Medical School, Chonju, South Korea.

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 (KATP) activity in single rat ventricular myocytes with 3 M KCl-filled conventional microelectrode and patch clamp techniques. KR-30450 (10(- 7) approximately 10(-5) M) reduced the action potential duration in a concentration-dependent manner and this was inhibited by 3 microM glibenclamide, suggesting that KATP was involved. In cell-attached patches, KR-30450 (10(-5) M) in the pipette activated the KATP which was closed by 3 microM glibenclamide. In inside-out patches, the effects of KR-30450 on KATP activity were examined before and after run- down of the channel. Before run-down, KR-30450 increased the KATP activity only in the presence of ATP and shifted the [ATP]i-KATP activity relationship to the right. After run-down, KR-30450 did not affect the KATP activity either in the presence or absence of 3 mM UDP, but increased the UDP-induced KATP activity in the presence of 1 mM ATP- gamma-S. From these results, we conclude that KR-30450 antagonizes the inhibitory effect of ATP on the KATP 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.

Volume 275, Issue 2, pp. 807-812, 11/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1995 by the American Society for Pharmacology and Experimental Therapeutics.