title: β1-Adrenergic blocker bisoprolol reverses down-regulated ion channels in sinoatrial node of heart failure rats.
abstract: Bisoprolol, an antagonist of β1-adrenergic receptors, is effective in reducing the morbidity and mortality in patients with heart failure (HF). It has been found that HF is accompanied with dysfunction of the sinoatrial node (SAN). However, whether bisoprolol reverses the decreased SAN function in HF and how the relevant ion channels in SAN change were relatively less studied. SAN function and messenger RNA (mRNA) expression of sodium channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits were assessed in sham-operated rats, abdominal arterio-venous shunt (volume overload)-induced HF rats, and bisoprolol- treated HF rats. SAN cells of rats were isolated by laser capture microdissection. Quantitative real-time PCR analysis was used to quantify mRNA expression of sodium channels and HCN channel subunits in SAN. Intrinsic heart rate declined and sinus node recovery time prolonged in HF rats, indicating the suppressed SAN function, which could be improved by bisoprolol treatment. Nav1.1, Nav1.6, and HCN4 mRNA expressions were reduced in SAN in HF rats compared with that in control rats. Treatment with bisoprolol could reverse both the SAN function and the Nav1.1, Nav1.6, and HCN4 mRNA expression partially. These data indicated that bisoprolol is effective in HF treatment partially due to improved SAN function by reversing the down-regulation of sodium channels (Nav1.1 and Nav1.6) and HCN channel (HCN4) subunits in SAN in failing hearts.
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Texas Heart Institute/St. Luke's Hospital, Section of Cardiology, University of Texas School of Medicine at Houston, Houston, TX, USA.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
authors.forename: Geru
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Han
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.|Shaanxi Key Laboratory of Molecular Cardiology, Xi'an Jiaotong University, Shaanxi, 710061, China.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, No.277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Ma
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, Shaanxi, 710061, China. tingzhong.wang@mail.xjtu.edu.cn.|Shaanxi Key Laboratory of Molecular Cardiology, Xi'an Jiaotong University, Shaanxi, 710061, China. tingzhong.wang@mail.xjtu.edu.cn.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, No.277 Yanta West Road, Xi'an, Shaanxi, 710061, China. tingzhong.wang@mail.xjtu.edu.cn.
authors.forename: Tingzhong
authors.initials: T
authors.lastname: Wang
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D064752:Atrial Remodeling / Q000187:drug effects; D017298:Bisoprolol / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D061346:Laser Capture Microdissection; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015221:Potassium Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012849:Sinoatrial Node / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D002316:Cardiotonic Agents; C513836:HCN4 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D015221:Potassium Channels; D021122:Protein Subunits; D012333:RNA, Messenger; C568250:Scn1a protein, rat; C507811:Scn8a protein, rat; D017298:Bisoprolol
keywords: Bisoprolol; HCN channel; Heart failure; Remodeling; Sinoatrial node; Sodium channel