title: Novel electropharmacological activity of amiodarone on human HCN channels heterologously expressed in the Xenopus oocytes.
abstract: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels underlie the pacemaker currents (I(f)) in cardiac cells. The objectives of this study were to investigate the electropharmacological activity of amiodarone on human HCN channels heterologously expressed in Xenopus laevis oocytes. hHCN channels were expressed in oocytes and studied using the standard two-electrode voltage-clamp techniques. The results show that amiodarone blocks hHCN channels heterologously expressed in the Xenopus oocytes in a concentration- and use-dependent manner, but doesn't modify the voltage dependence of activation and reversal potentials. And the removal of blockage of HCN channels by amiodarone was favored by inward current flow, not by hyperpolarizing potential. Characteristics of blockage on hHCN channels were consistent with those of amiodarone as "trapped" drugs on human ether-a-go-go-related gene (HERG) channels. These results will be useful for elucidating the potentially antiarrhythmic mechanism of amiodarone.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Fan
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Chen
authors.forename: Pan
authors.initials: P
authors.lastname: Wu
authors.forename: Junlian
authors.initials: J
authors.lastname: Xing
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Song
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Congxin
authors.initials: C
authors.lastname: Huang
mesh_terms: D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D014982:Xenopus laevis / Q000235:genetics
chemical_list: D000889:Anti-Arrhythmia Agents; D054815:Cyclic Nucleotide-Gated Cation Channels; D000638:Amiodarone