About half of the late sodium current in cardiac myocytes from dog ventricle is due to non-cardiac-type Na+ channels
About half of the late sodium current in cardiac myocytes from dog ventricle is due to non-cardiac-type Na+ channels
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DOI：
10.1016/j.yjmcc.2012.06.012
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发表时间：
2012-11-01
影响因子：
5
通讯作者：
Dumaine, Robert
中科院分区：
文献类型：
--
作者：
Biet, Michael;Barajas-Martinez, Hector;Dumaine, Robert
电压门控钠通道（Na（v）s）对于传播神经元和心脏电脉冲是必不可少的。虽然心脏Na+电流（I-Na）通常都归因于心脏亚型Na（v）1.5，但一些证据表明其他Na+通道亚型也在心室中表达。区分Na+通道的一种方法是通过它们对河豚毒素（TTX）的敏感性;与Na（v）1.5通道相比，各种“非心脏型”Na+通道对TTX（表示为tNa（v）通道）相对敏感。已在具有各种病理状况（例如肥大、梗塞和缺血）的心脏中检测到tNa（v）通道，其中它们可增强迟发Na+电流（I-NaL），从而在这些状况下延长动作电位（导致EKG上的QT间期延长）。本文的主要目的是评估在何种程度上非心脏同种型有助于I-NaL在正常生理条件下。用膜片钳技术测定急性分离的犬心肌细胞中的I-NaL。我们的研究结果表明，平均44%的晚期I-Na电流是由于非心脏Nays。先前的研究表明，在与各种心脏疾病相关的病理生理条件下，非心脏Na-v通道的过表达是导致心脏动作电位持续时间延长（从而导致QT间期延长）的原因。我们的发现表明，非心脏Nay通道是强有力的贡献者I-NaL在生理条件下，从而表明这些通道也是心脏动作电位的持续时间的主要决定因素，即使在健康的心脏。有趣的是，这些结果可能解释了遗传性神经元和肌肉骨骼疾病患者中与QT间期延长相关的心律失常的观察结果，这些疾病涉及增强非心脏型Na（v）s电流的突变，这种联系显然以前从未建立过。(C)2012爱思唯尔有限公司保留所有权利。
Voltage gated sodium channels (Na(v)s) are essential to propagate neuronal and cardiac electrical impulses. While the cardiac Na+ current (I-Na) is often all attributed to the cardiac isoform, Na(v)1.5, some evidence suggests that other Na+ channel isoforms are also expressed in the heart ventricle. One way to distinguish Na+ channels is by their sensitivity to tetrodotoxin (TTX); various "non-cardiac-type" Na+ channels are relatively sensitive to TTX (denoted tNa(v) channels) compared to Na(v)1.5 channels. tNa(v) channels have been detected in hearts with various pathological conditions such as hypertrophy, infarction and ischemia, where they might enhance the late Na+ current (I-NaL) thereby prolonging the action potential under such conditions (resulting in a prolonged QT interval on the EKG). The principal aim of this article is to evaluate the extent to which non-cardiac isotypes contribute to I-NaL under normal physiological conditions. I-NaL was measured in acutely dissociated dog cardiomyocytes using the patch-clamp technique. Our results indicate that 44% on average of the late I-Na current is due to non-cardiac Nays. Previous studies indicated that the overexpression of non-cardiac Na-v channels is responsible for the prolonged duration of the cardiac action potential (and, thereby, a prolonged QT interval) under pathophysiological conditions associated with various heart diseases. Our finding indicates that non-cardiac Nay channels are strong contributors to I-NaL under physiological conditions thereby suggesting that these channels are also major determinants of the duration of the cardiac action potential even in healthy hearts. Interestingly, these results may explain the observations of cardiac arrhythmias associated with prolonged QT intervals in people with inherited neuronal and musculoskeletal diseases involving mutations that enhance the current from non-cardiac-type Na(v)s, a connection which apparently was never made before. (C) 2012 Elsevier Ltd. All rights reserved.