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在生理条件下，重新评估动作电位上升速度作为心肌细胞中钠离子电流的测量指标。

Re-evaluation of the action potential upstroke velocity as a measure of the Na+ current in cardiac myocytes at physiological conditions.

机构信息

Department of Anatomy, Embryology, and Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

PLoS One. 2010 Dec 31;5(12):e15772. doi: 10.1371/journal.pone.0015772.

DOI:10.1371/journal.pone.0015772
PMID:21217835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3013114/
Abstract

BACKGROUND

The SCN5A encoded sodium current (I(Na)) generates the action potential (AP) upstroke and is a major determinant of AP characteristics and AP propagation in cardiac myocytes. Unfortunately, in cardiac myocytes, investigation of kinetic properties of I(Na) with near-physiological ion concentrations and temperature is technically challenging due to the large amplitude and rapidly activating nature of I(Na), which may seriously hamper the quality of voltage control over the membrane. We hypothesized that the alternating voltage clamp-current clamp (VC/CC) technique might provide an alternative to traditional voltage clamp (VC) technique for the determination of I(Na) properties under physiological conditions.

PRINCIPAL FINDINGS

We studied I(Na) under close-to-physiological conditions by VC technique in SCN5A cDNA-transfected HEK cells or by alternating VC/CC technique in both SCN5A cDNA-transfected HEK cells and rabbit left ventricular myocytes. In these experiments, peak I(Na) during a depolarizing VC step or maximal upstroke velocity, dV/dt(max), during VC/CC served as an indicator of available I(Na). In HEK cells, biophysical properties of I(Na), including current density, voltage dependent (in)activation, development of inactivation, and recovery from inactivation, were highly similar in VC and VC/CC experiments. As an application of the VC/CC technique we studied I(Na) in left ventricular myocytes isolated from control or failing rabbit hearts.

CONCLUSIONS

Our results demonstrate that the alternating VC/CC technique is a valuable experimental tool for I(Na) measurements under close-to-physiological conditions in cardiac myocytes.

摘要

背景

SCN5A 编码的钠电流（I(Na)）产生动作电位（AP）上升支，是心肌细胞中 AP 特征和 AP 传播的主要决定因素。不幸的是，由于 I(Na)的振幅大且激活迅速，在心肌细胞中，用接近生理离子浓度和温度来研究 I(Na)的动力学特性在技术上具有挑战性，这可能严重阻碍对膜电压的控制质量。我们假设交替电压钳-电流钳（VC/CC）技术可能为在生理条件下确定 I(Na)特性提供一种替代传统电压钳（VC）技术的方法。

主要发现

我们通过 VC 技术在 SCN5A cDNA 转染的 HEK 细胞中或通过交替 VC/CC 技术在 SCN5A cDNA 转染的 HEK 细胞和兔左心室心肌细胞中研究了接近生理条件下的 I(Na)。在这些实验中，去极化 VC 步骤期间的 I(Na)峰值或 VC/CC 期间的最大上升速度 dV/dt(max) 作为可用 I(Na)的指标。在 HEK 细胞中，I(Na)的生理特性，包括电流密度、电压依赖性（失活）、失活的发展和失活的恢复，在 VC 和 VC/CC 实验中高度相似。作为 VC/CC 技术的应用，我们研究了来自对照或衰竭兔心脏的左心室心肌细胞中的 I(Na)。

结论

我们的结果表明，交替 VC/CC 技术是在心肌细胞中接近生理条件下测量 I(Na)的一种有价值的实验工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/3a121165a4e3/pone.0015772.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/7f140b4b3525/pone.0015772.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/57ab5e13df7a/pone.0015772.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/7e26103dbb04/pone.0015772.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/0571ce25a592/pone.0015772.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/eec5b1ae6bc4/pone.0015772.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/3a121165a4e3/pone.0015772.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/7f140b4b3525/pone.0015772.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/57ab5e13df7a/pone.0015772.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/7e26103dbb04/pone.0015772.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/0571ce25a592/pone.0015772.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/eec5b1ae6bc4/pone.0015772.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/285d/3013114/3a121165a4e3/pone.0015772.g006.jpg

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