title: Hirsutenone directly blocks human ether-a-go-go related gene K+ channels.
abstract: The aim of the present study was to investigate whether hirsutenone affects the human ether-a-go-go related gene (hERG) K(+) channels. Many drugs promote formation of the acquired form of long QT syndrome (LQTS) by blocking the hERG K(+) channels. Hirsutenone, a new candidate for the treatment inflammatory skin lesions, induced a concentration-dependent decrease in hERG K(+) current amplitudes. Hirsutenone significantly decreased the time constants at the onset of inactivation. However, the reductions in the time constants of steady-state inactivation and the recovery from inactivation after hirsutenone treatment were not significant. In addition, the drug had no effect on the voltage-dependent activation curve or the steady-state inactivation curve. In summary, hirsutenone potentially acts as a blocker of hERG K(+) channels functioning by modifying the channel inactivation kinetics.
authors: Department of Physiology, College of Medicine, Chung-Ang University, Seoul 156–756, Korea.
authors: Jihyun
authors: J
authors: Yun
authors: Hyemi
authors: H
authors: Bae
authors: Sun Eun
authors: SE
authors: Choi
authors: Jung-Ha
authors: JH
authors: Kim
authors: Young Wook
authors: YW
authors: Choi
authors: Inja
authors: I
authors: Lim
authors: Chung Soo
authors: CS
authors: Lee
authors: Min Won
authors: MW
authors: Lee
authors: Jae-Hong
authors: JH
authors: Ko
authors: Seong Jun
authors: SJ
authors: Seo
authors: Hyoweon
authors: H
authors: Bang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016466:CHO Cells; D002396:Catechols / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D036381:Diarylheptanoids / Q000494:pharmacology*; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000893:Anti-Inflammatory Agents; D002396:Catechols; D036381:Diarylheptanoids; D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C508777:hirsutenone