Kwak Y G, Park S K, Kang H S, Kim J S, Chae S W, Cho K P, Yoo S E, Kim D
Department of Pharmacology, Chonbuk National University Medical School, Chonju, South Korea.
J Pharmacol Exp Ther. 1995 Nov;275(2):807-12.
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.
KR - 30450（2 - (2"(1",3"-二氧戊环)-2 - 甲基 - 4 - (2'-氧代 - 1'-吡咯烷基)-6 - 硝基 - 2H - 1 - 苯并芘）是一种新合成的苯并吡喃衍生物。我们采用3M KCl填充的传统微电极和膜片钳技术，研究了KR - 30450对离体大鼠乳头肌动作电位时程以及单个大鼠心室肌细胞中ATP敏感性钾通道（KATP）活性的影响。KR - 30450（10(-7) 至10(-5) M）以浓度依赖性方式缩短动作电位时程，且这种作用被3 microM格列本脲抑制，提示KATP参与其中。在细胞贴附式膜片中，移液管中的KR - 30450（10(-5) M）激活了被3 microM格列本脲关闭的KATP。在内外膜片模式下，在通道功能衰退前后研究了KR - 30450对KATP活性的影响。在功能衰退前，KR - 30450仅在ATP存在时增加KATP活性，并使[ATP]i - KATP活性关系向右移动。在功能衰退后，KR - 30450在3 mM UDP存在或不存在时均不影响KATP活性，但在1 mM ATP - γ - S存在时增加了UDP诱导的KATP活性。从这些结果，我们得出结论，KR - 30450以竞争性方式拮抗ATP对KATP 的抑制作用。KR - 30450的这些作用与ER - 001533和HOE - 234的作用相似，但与吡那地尔和雷马卡林的作用不同。
