Effects of autoantibodies againts β1-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca2+ currents

Abstract

Aim: To investigate the effects of autoantibodies against β1-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca2+ currents. Methods: Fifteen samples of autoantibodies against β 1-adrenoceptor positive sera of patients with hepatitis virus myocarditis were obtained and IgGs were purified by octanoic acid extraction. Binding of autoantibodies against β 1-adrenoceptor to guinea pig cardiac myocytes was examined by immunofluorescence. Using the patch clamp technique, the effects on the action potential and ICa-L of guinea pig cardiac myocytes caused by autoantibodies against β 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 β 1-adrenoceptor to guinea pig cardiomyocytes was observed. Autoantibodies against β1-adrenoceptor diluted at 1:80 prolonged APD20, APD50 and APD90 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 μmol/L metoprolol. Autoantibodies against β1-adrenoceptor diluted at 1:80, 1:100 and 1:120 significantly increased the ICa-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 β1-adrenoceptors (1 μmol/L metoprolol), autoantibodies against β 1-adrenoceptor diluted at 1:80 induced a slight increase of ICa-L peak amplitude only by 6.81±1.61%. A large number of cardiac myocytes exposed to high concentrations of autoantibodies against β1-adrenoceptor (1:80 and 1:100) were turned into rounded cells highly permeable to trypan blue. Conclusion: Autoantibodies against β1-adrenoceptor may result in arrhythmias and/or impairment of myocardiums in HVM, which would be mediated by the enhancement of ICa-L. Copyright © 2004 by The WJG Press.