Effects of autoantibodies against beta(1)-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca(2+) currents.
OBJECTIVE
To investigate the effects of autoantibodies against beta(1)-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca(2+) currents.


METHODS
Fifteen samples of autoantibodies against beta(1)-adrenoceptor positive sera of patients with hepatitis virus myocarditis were obtained and IgGs were purified by octanoic acid extraction. Binding of autoantibodies against beta(1)-adrenoceptor to guinea pig cardiac myocytes was examined by immunofluorescence. Using the patch clamp technique, the effects on the action potential and I(Ca-L) of guinea pig cardiac myocytes caused by autoantibodies against beta(1)-adrenoceptor in the absence and presence of metoprolol were investigated. Cell toxicity was examined by observing cell morphology and permeability of cardiac myocytes to trypan blue.


RESULTS
The specific binding of autoantibodies against beta(1)-adrenoceptor to guinea pig cardiomyocytes was observed. Autoantibodies against beta(1)-adrenoceptor diluted at 1:80 prolonged APD(20), APD(50) and APD(90) by 39.2%, 29.1% and 15.2% respectively, and only by 7.2%, 5.3% and 4.1% correspondingly in the presence of 1 micromol/L metoprolol. Autoantibodies against beta(1)-adrenoceptor diluted at 1:80, 1:100 and 1:120 significantly increased the I(Ca-L) peak current amplitude at 0 mV by 55.87+/-4.39%, 46.33+/-5.01% and 29.29+/-4.97% in a concentration-dependent manner. In contrast, after blocking of beta(1)-adrenoceptors (1 micromol/L metoprolol), autoantibodies against beta(1)-adrenoceptor diluted at 1:80 induced a slight increase of I(Ca-L) peak amplitude only by 6.81+/-1.61%. A large number of cardiac myocytes exposed to high concentrations of autoantibodies against beta(1)-adrenoceptor (1:80 and 1:100) were turned into rounded cells highly permeable to trypan blue.


CONCLUSIONS
Autoantibodies against beta(1)-adrenoceptor may result in arrhythmias and/or impairment of myocardiums in HVM, which would be mediated by the enhancement of I(Ca-L).
Liu
Kun
K
Department of Cardiology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
Liao
Yu-Hua
YH
Wang
Zhao-Hui
ZH
Li
Shu-Li
SL
Wang
Ming
M
Zeng
Ling-Lan
LL
Tang
Ming
M
D000200:Action Potentials / Q000187:drug effects / Q000276:immunology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism / Q000633:toxicity*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D006168:Guinea Pigs; D006518:Hepatitis Viruses; D066298:In Vitro Techniques; D008790:Metoprolol / Q000494:pharmacology; D009205:Myocarditis / Q000503:physiopathology* / Q000821:virology; D032383:Myocytes, Cardiac / Q000276:immunology* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011485:Protein Binding / Q000276:immunology; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*
D000319:Adrenergic beta-Antagonists; D001323:Autoantibodies; D020746:Calcium Channels, L-Type; D018342:Receptors, Adrenergic, beta-1; D008790:Metoprolol