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- adreno...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.展开更多
基金This work was supported by the National Basic Research Priorities Programme of China (No. G2000056906)the National Natural Science Foundation of China (No. 30270540 30171083).
基金Supported by the National Natural Science Foundation of China,NO.39970306
文摘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.
