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 (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.
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002478:Cells, Cultured; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006321:Heart / Q000502:physiology; D010654:Phenylbutyrates / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats
D001578:Benzopyrans; D006146:Guanidines; D010654:Phenylbutyrates; D015221:Potassium Channels; D011758:Pyrroles; D011760:Pyrrolidinones; D019806:Cromakalim; C074219:ER 001533; C096762:KR 30450; D000255:Adenosine Triphosphate; D005905:Glyburide