title: The calmodulin inhibitor and antipsychotic drug trifluoperazine inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.
abstract: We investigated the effect of the calmodulin inhibitor and antipsychotic drug trifluoperazine on voltage-dependent K(+) (Kv) channels. Kv currents were recorded by whole-cell configuration of patch clamp in freshly isolated rabbit coronary arterial smooth muscle cells. The amplitudes of Kv currents were reduced by trifluoperazine in a concentration-dependent manner, with an apparent IC50 value of 1.58±0.48 μM. The rate constants of association and dissociation by trifluoperazine were 3.73±0.33 μM(-1) s(-1) and 5.84±1.41 s(-1), respectively. Application of trifluoperazine caused a positive shift in the activation curve but had no significant effect on the inactivation curve. Furthermore, trifluoperazine provoked use-dependent inhibition of the Kv current under train pulses (1 or 2 Hz). These findings suggest that trifluoperazine interacts with Kv current in a closed state and inhibits Kv current in the open state in a time- and use-dependent manner, regardless of its function as a calmodulin inhibitor and antipsychotic drug.
authors: Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea.
authors: Da Hye
authors: DH
authors: Hong
authors: Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea.
authors: Youn Kyoung
authors: YK
authors: Son
authors: Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea.
authors: Hongliang
authors: H
authors: Li
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 Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 608-737, South Korea.
authors: Won-Kyo
authors: WK
authors: Jung
authors: Department of Bio-health Technology, Kangwon National University, Chuncheon 200-701, South Korea.
authors: Han Sol
authors: HS
authors: Kim
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: 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; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003331:Coronary Vessels / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors*; D011817:Rabbits; D014268:Trifluoperazine / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D002147:Calmodulin; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D014268:Trifluoperazine
keywords: Coronary artery; Trifluoperazine; Voltage-dependent K(+) channel