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电压依赖性钠通道的结构与功能:脑II型与心脏亚型的比较

Structure and function of voltage-dependent sodium channels: comparison of brain II and cardiac isoforms.

作者信息

Fozzard H A, Hanck D A

机构信息

Department of Pharmacological and Physiological Sciences, The University of Chicago, Illinois, USA.

出版信息

Physiol Rev. 1996 Jul;76(3):887-926. doi: 10.1152/physrev.1996.76.3.887.

DOI:10.1152/physrev.1996.76.3.887
PMID:8757791
Abstract

Cardiac and nerve Na channels have broadly similar functional properties and amino acid sequences, but they demonstrate specific differences in gating, permeation, ionic block, modulation, and pharmacology. Resolution of three-dimensional structures of Na channels is unlikely in the near future, but a number of amino acid sequences from a variety of species and isoforms are known so that channel differences can be exploited to gain insight into the relationship of structure to function. The combination of molecular biology to create chimeras and channels with point mutations and high-resolution electrophysiological techniques to study function encourage the idea that predictions of structure from function are possible. With the goal of understanding the special properties of the cardiac Na channel, this review examines the structural (sequence) similarities between the cardiac and nerve channels and considers what is known about the relationship of structure to function for voltage-dependent Na channels in general and for the cardiac Na channels in particular.

摘要

心脏和神经钠通道具有大致相似的功能特性和氨基酸序列,但它们在门控、通透、离子阻滞、调节和药理学方面表现出特定差异。在不久的将来不太可能解析钠通道的三维结构,但已知来自多种物种和亚型的一些氨基酸序列,因此可以利用通道差异来深入了解结构与功能的关系。分子生物学用于创建嵌合体和具有点突变的通道,以及高分辨率电生理技术用于研究功能,这促使人们认为从功能预测结构是可能的。为了理解心脏钠通道的特殊性质,本综述研究了心脏和神经通道之间的结构(序列)相似性,并考虑了一般电压依赖性钠通道特别是心脏钠通道的结构与功能关系的已知情况。

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