Effects of autoantibodies against β_1-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca^(2+) currents

AIM:To investigate the effects of autoantibodies against β_1-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca^(2+) 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 I_(ca-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 β_1-adrenoceptor diluted at 1:80 prolonged APO_(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 μmol/L metoprolol. Autoantibodies against β_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 β_1-adrenoceptors (1 μmol/L metoprolol),autoantibodies against β_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 β_1- adrenoceptor (1:80 and 1:100) were turned into rounded cells highly permeable to trypan blue. CONCLUSION:Autoantibodies against β_1-adrenoceptor may result in arrhythmias and/or impairment of myocardiums in HVM,which would be mediated by the enhancement of I_(ca-L.