Post-transcriptional alterations in the expression of cardiac Na+ channel subunits in chronic heart failure.
Post-transcriptional alterations in the expression of cardiac Na+ channel subunits in chronic heart failure.
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DOI：
10.1016/j.yjmcc.2004.04.003
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发表时间：
2004-07
影响因子：
5
通讯作者：
S. Zicha;V. Maltsev;S. Nattel;H. Sabbah;A. Undrovinas
中科院分区：
文献类型：
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作者：
S. Zicha;V. Maltsev;S. Nattel;H. Sabbah;A. Undrovinas
最近积累了关于Na+通道（NaCh）功能改变和缓慢心肌传导对于梗塞和衰竭心脏中的心律失常的重要性的临床和实验证据（即，心力衰竭，HF）。本研究评估了HF中Na+电流（INa）密度降低的基础NaCh亚基表达局部改变的分子机制。通过连续冠状动脉微栓塞在5只犬中诱导HF，并在末次栓塞后约3个月发生（左心室（LV），射血分数= 27 ± 7%）。5只正常犬作为对照组。酶法分离左室中层心肌细胞，全细胞膜片钳法测定心肌细胞的INa。通过竞争性逆转录聚合酶链反应分析编码心脏特异性NaCh α亚基Nav1.5及其辅助亚基β1（NaChβ1）的mRNA。通过蛋白质印迹法评估Nav1.5、NaChβ1和NaChβ2的蛋白质水平。与对照心脏相比，HF（n = 5）中INa/Cm的最大密度降低（33.2 ± 4.4 vs. 50.0 ± 4.9 pA/pF，平均值± S.E.M.，n = 5，P < 0.05）。与对照心脏相比，HF心脏中的稳态失活和激活的IN保持不变。FH中编码Nav1.5和NaChβ1的mRNA水平不变。而NaChβ1和NaChβ2蛋白在HF中的表达无明显变化。我们的结论是，实验性HF在狗的心脏NaCh α亚基表达的转录后变化的结果。
Clinical and experimental evidence has recently accumulated about the importance of alterations of Na+channel (NaCh) function and slow myocardial conduction for arrhythmias in infarcted and failing hearts (i.e., heart failure, HF). The present study evaluated the molecular mechanisms of local alterations in the expression of NaCh subunits which underlie Na+current (INa) density decrease in HF. HF was induced in five dogs by sequential coronary microembolization and developed approximately 3 months after the last embolization (left ventricle (LV), ejection fraction = 27 ± 7%). Five normal dogs served as a control group. Ventricular cardiomyocytes were isolated enzymatically from LV mid-myocardium and INawas measured by whole-cell patch-clamp. The mRNA encoding the cardiac-specific NaCh α-subunit Nav1.5, and one of its auxiliary subunits β1 (NaChβ1), were analyzed by competitive reverse transcription-polymerase chain reaction. Protein levels of Nav1.5, NaChβ1 and NaChβ2 were evaluated by western blotting. The maximum density of INa/Cmwas decreased in HF (n = 5) compared to control hearts (33.2 ± 4.4 vs. 50.0 ± 4.9 pA/pF, mean ± S.E.M., n = 5, P < 0.05). The steady-state inactivation and activation of INaremained unchanged in HF compared to control hearts. The levels of mRNA encoding Nav1.5, and NaChβ1 were unaltered in FH. However, Nav1.5 protein expression was reduced about 30% in HF, while NaChβ1 and NaChβ2 protein were unchanged. We conclude that experimental HF in dogs results in post-transcriptional changes in cardiac NaCh α-subunit expression.