title: The calmodulin inhibitor CGS 9343B inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.
abstract: We investigated the effects of the calmodulin inhibitor CGS 9343B on voltage-dependent K(+) (Kv) channels using whole-cell patch clamp technique in freshly isolated rabbit coronary arterial smooth muscle cells. CGS 9343B inhibited Kv currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC50) value of 0.81μM. The decay rate of Kv channel inactivation was accelerated by CGS 9343B. The rate constants of association and dissociation for CGS 9343B were 2.77±0.04μM(-1)s(-1) and 2.55±1.50s(-1), respectively. CGS 9343B did not affect the steady-state activation curve, but shifted the inactivation curve toward to a more negative potential. Train pulses (1 or 2Hz) application progressively increased the CGS 9343B-induced Kv channel inhibition. In addition, the inactivation recovery time constant was increased in the presence of CGS 9343B, suggesting that CGS 9343B-induced inhibition of Kv channel was use-dependent. Another calmodulin inhibitor, W-13, did not affect Kv currents, and did not change the inhibitory effect of CGS 9343B on Kv current. Our results demonstrated that CGS 9343B inhibited Kv currents in a state-, time-, and use-dependent manner, independent of calmodulin inhibition.
authors: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea.
authors: Hongliang
authors: H
authors: Li
authors: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea.
authors: Da Hye
authors: DH
authors: Hong
authors: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea.
authors: Han Sol
authors: HS
authors: Kim
authors: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea.
authors: Hye Won
authors: HW
authors: Kim
authors: Department of Biomedical Engineering, Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 608-737, South Korea.
authors: Won-Kyo
authors: WK
authors: Jung
authors: 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: Sung Hun
authors: SH
authors: Na
authors: Department of Immunology, Lab of Dendritic Cell Differentiation and Regulation, College of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors: In Duk
authors: ID
authors: Jung
authors: Department of Immunology, Lab of Dendritic Cell Differentiation and Regulation, College of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors: Yeong-Min
authors: YM
authors: Park
authors: Department of Microbiology, Inje University College of Medicine, Busan, 614-735, South Korea. Electronic address: cihima@inje.ac.kr.
authors: Il-Whan
authors: IW
authors: Choi
authors: 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: Won Sun
authors: WS
authors: Park
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003331:Coronary Vessels / Q000166:cytology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D001562:Benzimidazoles; D002147:Calmodulin; D026902:Potassium Channel Blockers; C052087:CGS 9343B
keywords: CGS 9343B; Calmodulin; Coronary artery; Use-dependency; Voltage-dependent K(+) channel