Fatjó Francesc, Sancho-Bru Pau, Fernández-Solà Joaquim, Sacanella Emilio, Estruch Ramón, Bataller Ramón, Nicolás Josep-María
Department of Internal Medicine, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
Alcohol Clin Exp Res. 2007 Jul;31(7):1099-105. doi: 10.1111/j.1530-0277.2007.00404.x. Epub 2007 May 4.
Excessive ethanol intake is one of the most frequent causes of acquired dilated cardiomyopathy in developed countries. L-type Ca(2+) channels, involved in excitation-contraction coupling, are disturbed in animal models of persistent ethanol consumption. This study was designed to evaluate the density and function of myocardial L-type Ca(2+) channel receptors in organ donors with chronic alcoholism and controls.
The protein expression of L-type Ca(2+) channels was determined with (3)H-(+)-PN 200-110-binding experiments using a specific antibody against the alpha(1)-subunit in homogenate samples of left-ventricle apex from organ donors: healthy controls (n=11), chronic alcoholic without cardiomyopathy (n=12), and alcoholics with cardiomyopathy (n=11). Morphometric measurements of cardiomyocytes were performed.
Binding experiments proved an up-regulation of L-type Ca(2+) channels expression in alcoholic patients compared with controls (B(max) 2.61 +/- 1.10 vs 1.33 +/- 0.49 fmol/mg, respectively; p<0.001). This up-regulation was present in the group of alcoholic subjects without cardiomyopathy, and was not seen in those with cardiomyopathy (3.39 +/- 2.20 vs 1.77 +/- 0.53 fmol/mg, respectively; p=0.02). The cross-sectional area and perimeter of the cells were greater in alcoholic patients with cardiomyopathy compared with controls and alcoholic patients without cardiomyopathy (500 +/- 87 vs 307 +/- 74 and 255 +/- 25 microm(2), respectively; p<0.001 both) as was the perimeter (78.7 +/- 7.7 vs 61.5 +/- 7.2 and 56.5 +/- 2.8 microm, respectively; p<0.001 both). Binding results did not change after adjusting receptor measurements for cross-sectional area and cell perimeter.
Chronic alcoholism causes an up-regulation of myocardial L-type Ca(2+) channel receptors, which decreases when cardiomyopathy is present.
在发达国家，过量摄入乙醇是获得性扩张型心肌病最常见的病因之一。参与兴奋 - 收缩偶联的L型Ca(2+)通道在持续摄入乙醇的动物模型中受到干扰。本研究旨在评估慢性酒精中毒器官供体和对照组中心肌L型Ca(2+)通道受体的密度和功能。
使用针对α(1)-亚基的特异性抗体，通过(3)H-(+)-PN 200-110结合实验测定器官供体左心室尖部匀浆样品中L型Ca(2+)通道的蛋白表达：健康对照组（n = 11）、无心肌病的慢性酒精中毒者（n = 12）和患有心肌病的酒精中毒者（n = 11）。对心肌细胞进行形态测量。
结合实验证明，与对照组相比，酒精中毒患者L型Ca(2+)通道表达上调（B(max)分别为2.61±1.10和1.33±0.49 fmol/mg；p<0.001）。这种上调在无心肌病的酒精中毒受试者组中存在，而在患有心肌病的受试者中未观察到（分别为3.39±2.20和1.77±0.53 fmol/mg；p = 0.02）。与对照组和无心肌病的酒精中毒患者相比，患有心肌病的酒精中毒患者细胞的横截面积和周长更大（分别为500±87 vs 307±74和255±25μm(2)；两者p<0.001），周长也是如此（分别为78.7±7.7 vs 61.5±7.2和56.5±2.8μm；两者p<0.001）。在对受体测量值进行横截面积和细胞周长校正后，结合结果没有变化。
慢性酒精中毒导致心肌L型Ca(2+)通道受体上调，而出现心肌病时该上调现象减弱。
