title: Pro-arrhythmic action of autoantibodies against the second extracellular loop of β1-adrenoceptor and its underlying molecular mechanisms.
abstract: OBJECTIVE
  The incidence of arrhythmia is associated with autoantibodies against the second extracellular loop of β1-adrenergic receptor (β1-AAbs). The current study was designed to determine the mechanisms by which arrhythmia experimentally might be induced by β1-AAbs.
  
  
  METHODS
  Blood samples were collected from patients with varied arrhythmias or coronary heart disease (CHD) and healthy subjects. The titer of β1-AAbs was assessed. Passive immunization rat models with β1-AAbs were established to determine whether β1-AAbs induced arrhythmia. Conventional intracellular microelectrode technique and whole cell patch clamp were employed to record action potential duration (APD), resting potential (RP), L-type calcium current (ICa-L), sodium-calcium exchange current (INCX), transient outward potassium current (Ito), inward rectifier potassium current (Ik1) and delayed rectifier potassium current (Ik).
  
  
  RESULTS
  High levels of β1-AAbs were found in the sera of heart disease patients, especially in ventricular arrhythmia (VA). Transfusion with β1-AAbs could induce arrhythmias in normal rats in vivo. β1-AAbs purified from the sera of active immunized rats induced triggered activity (TA), delayed after depolarization (DAD), and prolonged APD in the papillary muscles of rats. β1-AAbs prolonged QT interval, increased ICa-L and decreased IK1, Ito and INa-Ca in rat ventricular myocytes in vitro. All these effects can be inhibited by β1-AR blocker metoprolol.
  
  
  CONCLUSIONS
  These results demonstrate for the first time that β1-AAbs could directly induce ventricular arrhythmia by prolonging QT interval.
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, PR China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Du
authors.affiliation: Cardiac Electrophysiology Research Center, Medical College, Wuhan University of Science and Technology, Wuhan, Hubei 430000, PR China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, PR China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Bai
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: Bowei
authors.initials: B
authors.lastname: Wu
authors.affiliation: Emergency Medicine, Thomas Jefferson University, Philadelphia 19107, USA.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Diseases, Capital Medical University, Beijing 100069, PR China. Electronic address: liuhr2000@126.com.
authors.forename: Huirong
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D001323:Autoantibodies / Q000097:blood*; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008875:Middle Aged; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000097:blood* / Q000737:chemistry*
chemical_list: D001323:Autoantibodies; D018342:Receptors, Adrenergic, beta-1
keywords: Adrenergic receptor; Autoantibody; Beta1; QT prolongation; Ventricular arrhythmia