title: β1-Adrenoceptor autoantibodies affect action potential duration and delayed rectifier potassium currents in guinea pigs.
abstract: β1-Adrenoceptor autoantibodies (β1-AAs) affect the action potential duration (APD) in cardiomyocytes and are related to ventricular arrhythmias. The delayed rectifier potassium current (I K) plays a crucial role in APD, but the effects of β1-AAs on I K have not been completely illuminated. This work aimed to observe the effects of β1-AAs on I K and APD and further explore the mechanisms of β1-AA-mediated ventricular arrhythmias. β1-AAs were obtained from sera of patients with coronary heart disease (CHD) and nonsustained ventricular tachycardia. With whole-cell patch clamp technique, action potentials and I K were recorded. The results illustrated 0.1 μmol/L β1-AAs shortened APD at 50 % (APD50) and 90 % (APD90) of the repolarization. However, at 0.01 μmol/L, β1-AAs had no effects on either APD90 or APD50 (P > 0.05). At 0.001 μmol/L, β1-AAs significantly prolonged APD90 and APD50. Moreover, β1-AAs (0.001, 0.01, 0.1 μmol/L) dose-dependently increased the rapidly activating delayed rectifier potassium current (I Kr), but similarly decreased the slowly activating delayed rectifier potassium current (I Ks) and increased L-type calcium currents at the different concentrations. Taken together, the IKr increase induced by high β1-AA concentrations is responsible for a significant APD reduction which would contribute to repolarization changes and trigger the malignant ventricular arrhythmias in CHD patients.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Zhao
authors.forename: Haixia
authors.initials: H
authors.lastname: Huang
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Du
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Tingting
authors.initials: T
authors.lastname: Lv
authors.forename: Suli
authors.initials: S
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Wei
authors.forename: Jianyu
authors.initials: J
authors.lastname: Shang
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Huirong
authors.initials: H
authors.lastname: Liu
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D003327:Coronary Disease / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D017180:Tachycardia, Ventricular / Q000276:immunology / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D024661:Potassium Channels, Inwardly Rectifying; D018342:Receptors, Adrenergic, beta-1