Effects of autoantibodies against beta(1)-adrenoceptor in hepatitis virus myocarditis on action potential and L-type...

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

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.

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.

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).