title: Cisapride, a selective serotonin 5-HT4-receptor agonist, inhibits voltage-dependent K(+) channels in rabbit coronary arterial smooth muscle cells.
abstract: We investigated the effect of cisapride, a selective serotonin 5-HT4-receptor agonist, on voltage-dependent K(+) (Kv) channels using freshly isolated smooth muscle cells from the coronary arteries of rabbits. The amplitude of Kv currents was reduced by cisapride in a concentration-dependent manner, with an IC50 value of 6.77 ± 6.01 μM and a Hill coefficient of 0.51 ± 0.18. The application of cisapride shifted the steady-state inactivation curve toward a more negative potential, but had no significant effect on the steady-state activation curve. This suggested that cisapride inhibited the Kv channel in a closed state by changing the voltage sensitivity of Kv channels. The application of another selective serotonin 5-HT4-receptor agonist, prucalopride, did not affect the basal Kv current and did not alter the inhibitory effect of cisapride on Kv channels. From these results, we concluded that cisapride inhibited vascular Kv current in a concentration-dependent manner by shifting the steady-state inactivation curve, independent of its own function as a selective serotonin 5-HT4-receptor agonist.
authors: Department of Physiology, Kangwon National University, School of Medicine, Chuncheon, 200-701, South Korea.
authors: Hye Won
authors: HW
authors: Kim
authors: Department of Physiology, Kangwon National University, School of Medicine, Chuncheon, 200-701, South Korea.
authors: Hongliang
authors: H
authors: Li
authors: Department of Physiology, Kangwon National University, School of Medicine, Chuncheon, 200-701, South Korea.
authors: Han Sol
authors: HS
authors: Kim
authors: Department of Physiology, Kangwon National University, School of Medicine, Chuncheon, 200-701, South Korea.
authors: Sung Eun
authors: SE
authors: Shin
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 Molecular and Cellular Biochemistry, Kangwon National University, School of Medicine, Chuncheon, 200-701, South Korea.
authors: Kwon-Soo
authors: KS
authors: Ha
authors: Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University, School of Medicine, Chuncheon, 200-701, South Korea.
authors: Eun-Taek
authors: ET
authors: Han
authors: Department of Internal Medicine, Kangwon National University, School of Medicine, Chuncheon, 200-701, South Korea.
authors: Seok-Ho
authors: SH
authors: Hong
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; D001572:Benzofurans / Q000494:pharmacology; D020117:Cisapride / Q000494:pharmacology*; D003331:Coronary Vessels / Q000166:cytology*; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits; D011985:Receptors, Serotonin / Q000378:metabolism*
chemical_list: D001572:Benzofurans; D024642:Potassium Channels, Voltage-Gated; D011985:Receptors, Serotonin; C078730:serotonin 5 receptor; C406662:prucalopride; D020117:Cisapride
keywords: Cisapride; Coronary artery; Voltage-dependent K(+) channels