Liu Kun, Liao Yu-Hua, Wang Zhao-Hui, Li Shu-Li, Wang Ming, Zeng Ling-Lan, Tang Ming
Department of Cardiology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
World J Gastroenterol. 2004 Apr 15;10(8):1171-5. doi: 10.3748/wjg.v10.i8.1171.
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).
研究抗β1-肾上腺素能受体自身抗体在病毒性心肌炎中对动作电位和L型钙电流的影响。
获取15份病毒性心肌炎患者抗β1-肾上腺素能受体阳性血清样本，用辛酸提取法纯化IgG。采用免疫荧光法检测抗β1-肾上腺素能受体自身抗体与豚鼠心肌细胞的结合情况。运用膜片钳技术，研究在有无美托洛尔存在的情况下，抗β1-肾上腺素能受体自身抗体对豚鼠心肌细胞动作电位和L型钙电流（I（Ca-L））的影响。通过观察心肌细胞形态及对台盼蓝的通透性检测细胞毒性。
观察到抗β1-肾上腺素能受体自身抗体与豚鼠心肌细胞的特异性结合。抗β1-肾上腺素能受体自身抗体1:80稀释液分别使动作电位的20%复极时间（APD（20））、50%复极时间（APD（50））和90%复极时间（APD（90））延长39.2%、29.1%和15.2%，而在1 μmol/L美托洛尔存在时，相应延长仅为7.2%、5.3%和4.1%。抗β1-肾上腺素能受体自身抗体1:80、1:100和1:120稀释液以浓度依赖方式使0 mV时I（Ca-L）峰值电流幅度显著增加，分别增加55.87±4.39%、46.33±5.01%和29.29±4.97%。相反，在阻断β1-肾上腺素能受体（1 μmol/L美托洛尔）后，抗β1-肾上腺素能受体自身抗体1:80稀释液仅使I（Ca-L）峰值幅度轻微增加6.81±1.61%。大量暴露于高浓度抗β1-肾上腺素能受体自身抗体（1:80和1:100）的心肌细胞变成圆形，对台盼蓝高度通透。
抗β1-肾上腺素能受体自身抗体可能导致病毒性心肌炎患者出现心律失常和/或心肌损伤，这可能由L型钙电流增强介导。
