与蛙毒素结合丧失相关的点突变消除了钠通道亚型中的灰毒素效应。

Point-mutations related to the loss of batrachotoxin binding abolish the grayanotoxin effect in Na(+) channel isoforms.

作者信息

Ishii H, Kinoshita E, Kimura T, Yakehiro M, Yamaoka K, Imoto K, Mori Y, Seyama I

机构信息

Department of Physiology, School of Medicine, Hiroshima University, Hiroshima, 734-8551, Japan.

出版信息

Jpn J Physiol. 1999 Oct;49(5):457-61. doi: 10.2170/jjphysiol.49.457.

DOI:10.2170/jjphysiol.49.457

PMID:10603430

Abstract

The effect of grayanotoxin (GTX) on site-specific mutants of the alpha-subunit of rat skeletal muscle Na(+) channels (micro1) (micro1-I433K, micro1-N434K and micro1-L437K), which are resistant to batrachotoxin (BTX) (Wang and Wang (1998) Proc Natl Acad Sci USA, 95, 2653-2658) was studied using a whole-cell patch-clamp method. The GTX modification of the Na(+) channels was detected as a characteristic-sustained Na(+) current flow with repetitive pulses. We also studied the GTX action on mutants of the alpha-subunit of rat heart Na(+) channels (RH1) (RH1-V406K and RH1-L410K) which match with micro1-I433 and micro1-L437. All the mutants lost their sensitivity to GTX. This finding indicates that GTX may share a binding site with BTX in transmembrane segment I-S6 of two different Na(+) channel isoforms, micro1 and RH1.

摘要

使用全细胞膜片钳方法研究了灰藓毒素（GTX）对大鼠骨骼肌钠通道（micro1）α亚基的位点特异性突变体（micro1-I433K、micro1-N434K和micro1-L437K）的影响，这些突变体对蟾毒素（BTX）具有抗性（Wang和Wang（1998年）《美国国家科学院院刊》，95，2653 - 2658）。通过重复脉冲检测到的特征性持续钠电流来检测GTX对钠通道的修饰作用。我们还研究了GTX对大鼠心脏钠通道（RH1）α亚基突变体（RH1-V406K和RH1-L410K）的作用，这些突变体与micro1-I433和micro1-L437匹配。所有突变体均失去了对GTX的敏感性。这一发现表明，GTX可能在两种不同钠通道亚型micro1和RH1的跨膜段I-S6中与BTX共享一个结合位点。