The calmodulin inhibitor and antipsychotic drug trifluoperazine inhibits voltage-dependent K channels in rabbit coronary arterial smooth muscle cells |
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Authors: | Da Hye Hong Youn Kyoung Son Hongliang Li In Duk Jung Yeong-Min Park Won-Kyo Jung Han Sol Kim Il-Whan Choi Won Sun Park |
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Institution: | 1. Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea;2. Department of Immunology, Lab of Dendritic Cell Differentiation and Regulation, College of Medicine, Konkuk University, Chungju 380-701, South Korea;3. Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 608-737, South Korea;4. Department of Bio-health Technology, Kangwon National University, Chuncheon 200-701, South Korea;5. Department of Microbiology, Inje University College of Medicine, Busan 614-735, South Korea |
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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. |
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Keywords: | Trifluoperazine Voltage-dependent K+ channel Coronary artery |
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