title: W-7 inhibits voltage-dependent K(+) channels independent of calmodulin activity in rabbit coronary arterial smooth muscle cells.
abstract: We investigated the effect of W-7, a calmodulin inhibitor, on voltage-dependent K(+) (Kv) channels in freshly isolated coronary arterial smooth muscle cells using the whole-cell patch clamp technique. The amplitude of Kv currents was inhibited by W-7 in a concentration-dependent manner, with an IC50 value of 3.38±0.47μM and a Hill coefficient of 0.84±0.10. W-7 shifted the activation curve to a more positive potential but had no significant effect on the inactivation curve, which indicated that W-7 inhibited the Kv current in a closed state of the Kv channel. Another calmodulin inhibitor, W-13, had no significant effect on Kv currents and did not change the inhibitory effect of W-7 on Kv channels. From these results, we conclude that W-7 inhibited the Kv current in a dose-dependent manner, but this inhibition occurred independent of calmodulin activity and in a closed (inactivated) state of the Kv channels.
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Microbiology, Inje University College of Medicine, Busan 614-735, South Korea.
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea.
authors.forename: Da Hye
authors.initials: DH
authors.lastname: Hong
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea.
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
authors.affiliation: Institute of Medical Sciences, Department of Obstetrics and Gynecology, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Sung Hun
authors.initials: SH
authors.lastname: Na
authors.affiliation: Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus) Pukyong National University, Busan 608-737, South Korea.
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Firth
authors.affiliation: Department of Immunology, Lab of Dendritic Cell Differentiation and Regulation, College of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.affiliation: Department of Immunology, Lab of Dendritic Cell Differentiation and Regulation, College of Medicine, Konkuk University, Chungju 380-701, South Korea. Electronic address: immun3023@kku.ac.kr.
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea. Electronic address: parkws@kangwon.ac.kr.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
mesh_terms: D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D003331:Coronary Vessels / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D002147:Calmodulin; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; C017967:W 7
keywords: Coronary artery; Voltage-dependent K(+) channel; W-13 (CID:16760706); W-7; W-7 (CID:124887)