title: Serum albumin attenuates the open-channel blocking effects of propofol on the human Kv1.5 channel.
abstract: The intravenous anesthetic propofol modulates various ion channel functions. It is generally accepted that approximately 98% of propofol binds to blood constituents and that the free (unbound) drug preferentially affects target proteins including ion channels. However, modulatory effects of propofol on ion channels have not been previously explored in the presence of serum albumin. This study was designed to investigate the effects of serum albumin on the blocking action of propofol on the human Kv1.5 (hKv1.5) current. Whole-cell patch-clamp method was used to record the hKv1.5 channel current, heterologously expressed in Chinese hamster ovary cells, in the absence and presence of bovine serum albumin (BSA). Propofol induced a time-dependent decline of the hKv1.5 current during depolarizing steps and slowed the time course of tail current decay upon repolarization, supporting that propofol acts as an open-channel blocker. This blocking effect was reversible and concentration-dependent with an IC50 of 62.9±3.1μM (n = 6). Bath application of 1% BSA markedly reduced the blocking potency of propofol on hKv1.5 current (IC50 of 1116.0±491.4μM; n = 6). However, in the presence of BSA, the propofol-induced inhibition of hKv1.5 current was also accompanied by a gradual decline of activated current during depolarization and deceleration of deactivating tail current upon repolarization. The presence of BSA greatly attenuated the blocking potency of propofol on hKv1.5 channel without affecting the mode of action of propofol on the channel. Serum albumin thus appears to bind to propofol and thereby reducing effective concentrations of the drug for inhibition of hKv1.5 channel.
authors.affiliation: Department of Anesthesiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan. Electronic address: akiko77@belle.shiga-med.ac.jp.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kojima
authors.affiliation: Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors.forename: Jia-Yu
authors.initials: JY
authors.lastname: Bai
authors.affiliation: Department of Anesthesiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors.forename: Wei-Guang
authors.initials: WG
authors.lastname: Ding
authors.affiliation: Department of Anesthesiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Kitagawa
authors.affiliation: Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan. Electronic address: matuurah@belle.shiga-med.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuura
mesh_terms: D000818:Animals; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D055724:Electrophysiological Phenomena / Q000187:drug effects; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D015742:Propofol / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000494:pharmacology*
chemical_list: D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D012710:Serum Albumin, Bovine; D015742:Propofol
keywords: Kv1.5; Open-channel block; Propofol; Serum albumin; hKv1.5