Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle.
Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle.
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DOI：
10.1016/j.yjmcc.2009.07.017
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发表时间：
2010-01
影响因子：
5
通讯作者：
Cordeiro JM
中科院分区：
文献类型：
--
作者：
Calloe K;Soltysinska E;Jespersen T;Lundby A;Antzelevitch C;Olesen SP;Cordeiro JM
目的：研究犬左心室瞬时外向电流(Ito)激活剂NS5806的电生理和分子特性。采用全细胞膜片钳技术测定分离的心外膜(Epi)、中层心肌(Mid)和心内膜(Endo)细胞的Ito。本文还研究了NS5806对CHO-K1细胞和非洲爪哇卵母细胞Kv4.3电流的激活作用。在共转染Kv4.3和KChIP2的CHO-K1细胞中，NS5806(10μM)使电流幅度增加35%，电流衰减明显减慢，τ由7.0±0.4ms增加到10.2±0.3ms。在没有KChIP2的情况下，电流衰减不受NS5806的影响。在心室肌细胞中，NS5806使外周、中段和内膜肌细胞的Ito密度分别增加80%、82%和16%(+40 mV)，并使稳态失活转变为负电位。NS5806还显著延缓了Ito的衰变，使Epi、Mid和Endo细胞的总电荷分别增加到对照组的227%、192%和83%(+40 mV，p<；0.05)。Kv4.3和KChIP2mRNA在3种类型的心室细胞中的定量结果显示，Kv4.3的表达水平是一致的，而KChIP2在Epi和Mid细胞中的表达水平显着增加。蛋白质印迹结果证实了KChIP2梯度的存在。我们的结果表明，NS5806通过增加电流密度和减缓衰减来增强Ito，并且这两者都依赖于KChIP2的存在。在Epi和Mid细胞中，Ito和NS5806的增强作用最大，因为KChIP2水平在这些细胞类型中最高。
To examine the electrophysiological and molecular properties of the transient outward current (Ito) in canine left ventricle using a novel Ito activator, NS5806. Ito was measured in isolated epicardial (Epi), midmyocardial (Mid) and endocardial (Endo) cells using whole-cell patch-clamp techniques. NS5806 activation of Kv4.3 current was also studied in CHO-K1 cells and Xenopus laevis oocytes. In CHO-K1 cells co-transfected with Kv4.3 and KChIP2, NS5806 (10 μM) caused a 35 % increase in current amplitude and a marked slowing of current decay with τ increasing from 7.0±0.4 to 10.2±0.3 ms. In the absence of KChIP2, current decay was unaffected by NS5806. In ventricular myocytes, NS5806 increased Ito density by 80%, 82%, and 16% in Epi, Mid, and Endo myocytes, respectively (at +40 mV) and shifted steady-state inactivation to negative potentials. NS5806 also significantly slowed decay of Ito, increasing total charge to 227%, 192% and 83% of control in Epi, Mid and Endo cells, respectively (+40 mV, p<0.05). Quantification of Kv4.3 and KChIP2 mRNA in the 3 ventricular cell types revealed that levels of Kv4.3 message was uniform but those of KChIP2 were significantly greater in Epi and Mid cells. The KChIP2 gradient was confirmed at the protein level by Western blot. Our results suggest that NS5806 augments Ito by increasing current density and slowing decay and that both depend on the presence of KChIP2. Ito and its augmentation by NS5806 are greatest in Epi and Mid cells because KChIP2 levels are highest in these cell types.
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影响因子：
10.8
作者：
Radicke, Susanne;Cotella, Diego;Wettwer, Erich
通讯作者：
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影响因子：
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作者：
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