title: Open channel block of Kv1.3 by rosiglitazone and troglitazone: Kv1.3 as the pharmacological target for rosiglitazone.
abstract: The effects of rosiglitazone and troglitazone were examined on cloned Kv1.3 channels stably expressed in Chinese hamster ovary cells using the whole-cell configuration of the patch-clamp technique. Rosiglitazone decreased the Kv1.3 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an IC(50) of 18.6 microM. These effects were reversible after washout of the drug. Troglitazone caused the block of Kv1.3 with a similar pattern but was five times more potent than rosiglitazone with an IC(50) of 3.5 microM. The block of Kv1.3 by rosiglitazone and troglitazone was voltage-dependent at a membrane potential coinciding with the activation of the channels. Both drugs decreased the tail current amplitude and slowed the deactivation process of Kv1.3, resulting in a tail crossover phenomenon. These results indicate that rosiglitazone and troglitazone block the open state of Kv1.3 channels, suggesting that it is an important pharmacological target for rosiglitazone as a potent blocker of Kv1.3 channels.
authors.affiliation: Department of Physiology, Medical Research Center, College of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Socho-Gu, Seoul, South Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Ahn
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Jang
authors.forename: Myung-Jun
authors.initials: MJ
authors.lastname: Kim
authors.forename: Duck-Joo
authors.initials: DJ
authors.lastname: Rhie
authors.forename: Shin-Hee
authors.initials: SH
authors.lastname: Yoon
authors.forename: Yang-Hyeok
authors.initials: YH
authors.lastname: Jo
authors.forename: Myung-Suk
authors.initials: MS
authors.lastname: Kim
authors.forename: Ki-Wug
authors.initials: KW
authors.lastname: Sung
authors.forename: Seong Yun
authors.initials: SY
authors.lastname: Kim
authors.forename: Sang June
authors.initials: SJ
authors.lastname: Hahn
mesh_terms: D000818:Animals; D016466:CHO Cells; D002839:Chromans / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002839:Chromans; D051664:Kv1.3 Potassium Channel; D045162:Thiazolidinediones; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D000077288:Troglitazone