Back to Search
Start Over
Pro-arrhythmic action of autoantibodies against the second extracellular loop of β1-adrenoceptor and its underlying molecular mechanisms.
- Source :
-
International Journal of Cardiology . Nov2015, Vol. 198, p251-258. 8p. - Publication Year :
- 2015
-
Abstract
- Objectives The incidence of arrhythmia is associated with autoantibodies against the second extracellular loop of β 1 -adrenergic receptor (β 1 -AAbs). The current study was designed to determine the mechanisms by which arrhythmia experimentally might be induced by β 1 -AAbs. Methods Blood samples were collected from patients with varied arrhythmias or coronary heart disease (CHD) and healthy subjects. The titer of β 1 -AAbs was assessed. Passive immunization rat models with β 1 -AAbs were established to determine whether β 1 -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 ( I Ca-L ), sodium–calcium exchange current (INCX), transient outward potassium current ( I to ), inward rectifier potassium current ( I k1 ) and delayed rectifier potassium current ( I k ). Results High levels of β 1 -AAbs were found in the sera of heart disease patients, especially in ventricular arrhythmia (VA). Transfusion with β 1 -AAbs could induce arrhythmias in normal rats in vivo. β 1 -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. β 1 -AAbs prolonged QT interval, increased I Ca-L and decreased I K1 , I to and I Na–Ca in rat ventricular myocytes in vitro. All these effects can be inhibited by β 1 -AR blocker metoprolol. Conclusions These results demonstrate for the first time that β 1 -AAbs could directly induce ventricular arrhythmia by prolonging QT interval. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01675273
- Volume :
- 198
- Database :
- Academic Search Index
- Journal :
- International Journal of Cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 109104054
- Full Text :
- https://doi.org/10.1016/j.ijcard.2015.06.144