背景：肾素-血管紧张素-醛固酮系统可通过多种病理条件来影响心脏细胞形态和功能。本研究揭示醛固酮对心肌细胞表达缝隙连接蛋白Cx43的影响。
方法与结果：培养好的乳鼠期大鼠心肌细胞暴露于醛固酮24小时，检测Cx43蛋白和mRNA表达量。通过多电极阵列系统（Med-64）检测刺激全过程。用10-8mol/L的醛固酮处理心肌细胞，其Cx43
增加1.5倍，mRNA增加1.2倍 。Cx43免疫反应信号也有所增加。传导速度(CV) 增加了 24 % 。用较高浓度（ 10-6
-10-4mol/L）醛固酮处理肌细胞，其Cx43蛋白减少0.3倍 ，但Cx43 mRNA水平保持不变， CV降低了23 %
。经依普利酮预处理的肌细胞，再经10-8mol/L的醛固酮处理，Cx43不增加，CV也不增加，但米非司酮对其不产生此影响。经依普利酮或米非司酮预处理的心肌细胞，再经10-6
到10-4mol/L醛固酮处理，其Cx43表达量减少。
结论：醛固酮可能是通过对表达Cx43的双重影响来参与心律失常间隙连接重构的。
Effects of aldosterone on cx43 gap junction expression in neonatal rat cultured cardiomyocytes.
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine.
Background: The renin-angiotensin-aldosterone system affects cellular morphology and function in the heart under a variety of pathologic conditions. In the present study the effects of aldosterone on the expression of connexin (Cx) 43 gap junctions in cardiomyocytes were investigated. Methods and Results: Cultured rat ventricular myocytes were exposed to aldosterone for 24 h. The protein and mRNA expression of Cx43 was estimated. Propagation of excitation was visualized by a multiple electrode array system. Treatment of the myocytes with 10(-8) mol/L aldosterone resulted in a significant upregulation of Cx43 (by ~1.5-fold in protein and by ~1.2-fold in mRNA). The immunoreactive signal of Cx43 was also increased. Conduction velocity (CV) was increased by ~24%. Treatment of the myocytes with aldosterone at higher concentrations (10(-6)-10(-4) mol/L) caused a significant downregulation of Cx43 protein (by ~0.3-fold) without affecting Cx43 mRNA levels, and decreased the CV by ~23%. The Cx43 upregulation and CV acceleration at 10(-8) mol/L aldosterone were prevented by pretreatment with eplerenone, but unaffected by mifepristone. Pretreatment of the myocytes with eplerenone or mifepristone did not prevent the Cx43 downregulation by aldosterone at 10(-6)-10(-4) mol/L. Conclusions: Aldosterone may be involved in arrhythmogenic gap junction remodeling through its dual effects on the expression of Cx43. (Circ J 2009; 73: 1504 - 1512).
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