title: The Ca(2+) channel inhibitor efonidipine decreases voltage-dependent K(+) channel activity in rabbit coronary arterial smooth muscle cells.
abstract: The effect of efonidipine, a commercially available antihypertensive drug and Ca(2+) channel inhibitor, on voltage-dependent K(+) (Kv) channels was studied in freshly isolated rabbit coronary arterial smooth muscle cells using the whole-cell patch clamp technique. The amplitude of Kv current was decreased by application of efonidipine in a dose-dependent manner, with IC50 of 0.26μM and a Hill coefficient of 0.91, which suggests 1:1 binding stoichiometry. Efonidipine did not affect voltage-dependent activation of the Kv channel, but shifted the inactivation curve by -8.87mV. The inhibitory effect of efonidipine was not significantly changed by depletion of extracellular Ca(2+) or intracellular ATP, which indicated no involvement of the Ca(2+) channel or intracellular protein kinase-dependent cascades. We conclude that efonidipine dose-dependently inhibits Kv current in a phosphorylation- and Ca(2+) channel-independent manner.
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea.
authors.forename: Mi-Hyeong
authors.initials: MH
authors.lastname: Park
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
authors.forename: Da Hye
authors.initials: DH
authors.lastname: Hong
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.forename: Dae-Joong
authors.initials: DJ
authors.lastname: Kim
authors.forename: Haena
authors.initials: H
authors.lastname: Lee
authors.forename: Hyoweon
authors.initials: H
authors.lastname: Bang
authors.forename: Sung Hun
authors.initials: SH
authors.lastname: Na
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Jo
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009596:Nitrophenols / Q000008:administration & dosage / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; C066425:efonidipine
keywords: Coronary artery; Efonidipine; Voltage-dependent K(+) channels