Aldosterone increases voltage-gated sodium current in ventricular myocytes
Aldosterone increases voltage-gated sodium current in ventricular myocytes
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DOI：
10.1152/ajpheart.01060.2005
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发表时间：
2006-06-01
影响因子：
4.8
通讯作者：
Abriel, Hugues
中科院分区：
文献类型：
--
作者：
Boixel, Christophe;Gavillet, Bruno;Abriel, Hugues
醛固酮在心力衰竭（HF）发病机制中的作用仍知之甚少。近年来，研究表明醛固酮可调节心脏Ca ~（2+）和K ~+通道的功能，从而在电重构过程中发挥作用。本工作的目的是研究醛固酮对心脏Na+电流（I-Na）的作用。采用全细胞膜片钳技术，观察了醛固酮对成年小鼠心室肌细胞钠离子浓度的影响。在与1 μ M醛固酮孵育24小时后，I-Na密度显著增加（+55%），而生物物理性质和细胞膜电容没有改变。醛固酮（10 nM）使I-Na增加23%。在24小时共孵育实验中，使用放线菌素D，放线菌酮，或布雷菲德菌素A，醛固酮对I-Na的影响被废除。螺内酯（盐皮质激素受体拮抗剂，10 μ M）防止1 μ M醛固酮依赖性I-Na增加，而RU-38486（糖皮质激素受体拮抗剂，10 μ M）没有。动作电位时程（APD）在醛固酮处理的心肌细胞中比对照组延长（APD（90）：+53%）。此外，L型Ca 2+电流也上调（+48%）。我们进行了定量RT-PCR测量和Western印迹，以定量Na（v）1.5和Ca（v）1.2的mRNA和蛋白水平。（介导心脏I-Na和I-Ca的主要通道），但没有发现显著差异。总之，这项研究表明，醛固酮上调心脏I-Na，并表明这种现象可能有助于HF-诱导的电重构过程，可以逆转螺内酯。
The role of aldosterone in the pathogenesis of heart failure (HF) is still poorly understood. Recently, aldosterone has been shown to modulate the function of cardiac Ca2+ and K+ channels, thus playing a role in the electrical remodeling process. The goal of this work was to investigate the role of aldosterone on the cardiac Na+ current (I-Na). We analyzed the effects of aldosterone on I-Na in isolated adult mouse ventricular myocytes, using the whole cell patch-clamp technique. After 24 h incubation with 1 mu M aldosterone, the I-Na density was significantly increased (+55%), without alteration of the biophysical properties and the cell membrane capacitance. Aldosterone (10 nM) increased the I-Na by 23%. In 24-h coincubation experiments, with the use of actinomycin D, cycloheximide, or brefeldin A, the effect of aldosterone on I-Na was abolished. Spironolactone (mineralocorticoid receptor antagonist, 10 mu M) prevented the 1 mu M aldosterone-dependent I-Na increase, whereas RU-38486 (glucocorticoid receptor antagonist, 10 mu M) did not. The action potential duration (APD) was longer in aldosterone-treated (APD(90): +53%) than in control myocytes. In addition, the L-type Ca2+ current was also upregulated (+48%). We performed quantitative RT-PCR measurements and Western blots to quantify the mRNA and protein levels of Na(v)1.5 and Ca(v)1.2 (main channels mediating cardiac I-Na and I-Ca), but no significant difference was found. In conclusion, this study shows that aldosterone upregulates the cardiac I-Na and suggest that this phenomenon may contribute to the HF-induced electrical remodeling process that may be reversed by spironolactone.