title: Berberine attenuates spontaneous action potentials in sinoatrial node cells and the currents of human HCN4 channels expressed in Xenopus laevis oocytes.
abstract: The present study investigated the electropharmacological effects of a traditional Chinese herbal drug, berberine, on the spontaneous activity of sinoatrial nodes (SANs) of the rabbit heart and on human hyperpolarization-activated cyclic nucleotide-gated 4 (hHCN4) channels, which are heterologously expressed in xenopus oocytes, and which contribute to pacemaker currents (Ifs). A standard microelectrode technique and standard two‑electrode voltage‑clamp recordings were employed to examine the properties of transmembrane potentials and cloned hHCN4 subunit currents, respectively, under control conditions and berberine administration. Berberine decreased the rate of pacemaker firing and the rate of diastolic depolarization, and modified the action potential parameters. In addition, berberine suppressed the hHCN4 channel currents in a concentration‑ (1‑300 µM) and use‑dependent manner, and simultaneously decreased the activation and deactivation kinetics of the hHCN4 channels. The ability of berberine to modulate the If of cardiac pacemaker cells may contribute to its antiarrhythmic action.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Taihui
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Congxin
authors.initials: C
authors.lastname: Huang
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects; D009865:Oocytes; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D000889:Anti-Arrhythmia Agents; D004365:Drugs, Chinese Herbal; C119587:HCN4 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009124:Muscle Proteins; D015221:Potassium Channels; D001599:Berberine