On site of action of grayanotoxin in domain 4 segment 6 of rat skeletal muscle sodium channel

FEBS Letters

Seyama, Issei¹  Yakehiro, Masuhide²  Kimura, Takahiro¹  Yamaoka, Kaoru¹  Yuki, Tsunetsugu¹  Kinoshita, Eiji¹ 

[1] Department of Physiology, School of Medicine, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan;Division of Physiology, Department of Clinical Engineering, Hiroshima International University, Faculty of Health Sciences, 555-36 Gakuendai, Kurose-cho, Kamo-gun, Hiroshima Prefecture 732-0695, Japan

关键词: Grayanotoxin;    Binding site;    Na+ channel;    Batrachotoxin;    Domain 4 segment 6;    BTX;    batrachotoxin;    D;    domain;    GTX;    grayanotoxin;    HEK 293;    the tsA-201 subclone of human embryonic kidney cells;    I-V curve;    current-voltage relationship;    μ1;    α-subunit of rat skeletal muscle Na+ channel;    RBIIA;    α-subunit of rat brain type II Na+ channel;    S;    segment;    WT;    wild-type;    each mutant channel will be referenced by the original amino acid followed by its number and introduced amino acid;   

DOI  :  10.1016/S0014-5793(99)01715-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Grayanotoxin I (GTX I) is a diterpenoid extracted from the family of Ericaceae that binds to Na⁺ channels and causes persistent activation. We investigated the interaction of GTX I with the amino acid residues I1575, F1579 and Y1586 in transmembrane segment D4S6 of μ1. In F1579A, GTX shifted the threshold potential about 50 mV in the hyperpolarizing direction and modified Na⁺ channels twice as efficiently as that in wild-type. In contrast, these GTX-effects were eliminated completely in the I1575A mutant and were reduced substantially in mutant Y1586A. Lysine substitution for F1579 significantly reduced and for Y1586 completely eradicated the GTX-effect. Our data suggest that the GTX receptor site shares overlapping but non-identical molecular determinants with BTX in D4S6 and has common molecular determinants in D1S6.

【 授权许可】

Unknown