A transient outward potassium current activator recapitulates the electrocardiographic manifestations of Brugada syndrome.
A transient outward potassium current activator recapitulates the electrocardiographic manifestations of Brugada syndrome.
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瞬时外向钾电流激活剂概括了布鲁格达综合征的心电图表现。
DOI：
10.1093/cvr/cvn339
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发表时间：
2009-03-01
影响因子：
10.8
通讯作者：
Antzelevitch C
中科院分区：
文献类型：
--
作者：
Calloe K;Cordeiro JM;Di Diego JM;Hansen RS;Grunnet M;Olesen SP;Antzelevitch C
瞬时外向钾电流（Ito）被认为是激活剂的中心，但不是Brugada综合征（BrS）的发病机制。然而，伊藤可用来验证这一假设。在这里，我们提供了一个直接测试的假设，使用一种新的伊藤激活剂，NS 5806。使用离体犬心室肌细胞和冠状动脉灌注楔形制剂。全细胞膜片钳研究显示，NS 5806（10 μM）使+40 mV处的峰值Ito增加79±4%（24.5±2.2至43.6±3.4 pA/pF，n=7），并使失活时间常数从12.6±3.2减慢至20.3±2.9 ms，n=7。Ito携带的总电荷增加了186%（从363.9 ± 40.0增加到1042.0 ± 103.5 pA ms/pF，n=7）。在心室楔形准备中，NS 5806增加心外膜而非心内膜动作电位（AP）的1相和切迹振幅，并加重ECG J波，导致2相折返和多形性室性心动过速的发展（n=9）。虽然钠和钙通道阻滞剂能够诱导BrS仅在右心室楔制备，伊藤激活剂能够诱导楔从两个心室的表型。NS 5806在4/6例右心室和2/10例左心室楔形标本中诱导BrS。Ito激活剂NS 5806概括了BrS的电图和脑电图表现，为支持其在疾病发生中的关键作用提供了证据。我们的研究结果还表明，遗传缺陷导致伊藤功能的增益可以解释BrS的变体，其中ST段抬高或J波在右和左ECG导联中都很明显。
Transient outward potassium current (Ito) is thought to be central to the activator has not been pathogenesis of the Brugada syndrome (BrS). However, an Ito available with which to validate this hypothesis. Here we provide a direct test of the hypothesis using a novel Ito activator, NS5806. Isolated canine ventricular myocytes and coronary-perfused wedge preparations were used. Whole-cell patch-clamp studies showed that NS5806 (10 μM) increased peak Ito at +40 mV by 79±4% (24.5±2.2 to 43.6±3.4 pA/pF, n=7) and slowed the time-constant increased of inactivation from 12.6±3.2 to 20.3±2.9 ms, n=7. Total charge carried by Ito by 186% (from 363.9 ± 40.0 to 1042.0 ± 103.5 pA ms/pF, n=7). In ventricular wedge preparations, NS5806 increased phase 1 and notch amplitude of the action potential (AP) in epicardium, but not endocardium, and accentuated the ECG J-wave, leading to the development of phase 2 reentry and polymorphic ventricular tachycardia (n=9). While sodium and calcium channel blockers are capable of inducing BrS only in right ventricular wedge preparations, the Ito activator was able to induce the phenotype in wedges from both ventricles. NS5806 induced BrS in 4/6 right and 2/10 left ventricular wedge preparations. The Ito activator NS5806 recapitulates the electrographic and arrhythmic manifestation of BrS, providing evidence in support of its pivotal role in the genesis of the disease. Our findings also suggest that a genetic defect leading to a gain of function of Ito could explain variants of BrS in which ST-segment elevation or J-waves are evident in both right and left ECG leads.
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DOI：
10.1111/j.1540-8167.2000.tb00743.x
发表时间：
2000-01-01
影响因子：
2.7
作者：
Kalla, H;Yan, GX;Marinchak, R
通讯作者：
Marinchak, R
影响因子：
8.4
作者：
Delpon, Eva;Cordeiro, Jonathan M.;Antzelevitch, Charles
通讯作者：
Antzelevitch, Charles
DOI：
10.1152/ajpheart.1996.271.2.h548
发表时间：
1996-08-01
影响因子：
4.8
作者：
DiDiego, JM;Sun, ZQ;Antzelevitch, C
通讯作者：
Antzelevitch, C
影响因子：
37.8
作者：
Yan, GX;Antzelevitch, C
通讯作者：
Antzelevitch, C
影响因子：
5.5
作者：
Ogawa, M;Kumagai, K;Saku, K
通讯作者：
Saku, K