کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2063977 | 1544116 | 2016 | 4 صفحه PDF | دانلود رایگان |
• The marine toxin gambierol and 1-butanol do not compete as inhibitors of the Shaker Kv channel.
• Gambierol and 1-butanol are gating modifiers that induce channel inhibition by stabilizing a non-conducting conformation.
• The Shaker pore mutant P475A remains sensitive to gambierol displaying nanomolar affinity.
• Pore mutation T469V reduces Shaker's sensitivity to gambierol but does not affect the response to 1-butanol.
The marine polycyclic-ether toxin gambierol and 1-butanol (n-alkanol) inhibit Shaker-type Kv channels by interfering with the gating machinery. Competition experiments indicated that both compounds do not share an overlapping binding site but gambierol is able to affect 1-butanol affinity for Shaker through an allosteric effect. Furthermore, the Shaker-P475A mutant, which inverses 1-butanol effect, is inhibited by gambierol with nM affinity. Thus, gambierol and 1-butanol inhibit Shaker-type Kv channels via distinct parts of the gating machinery.
Journal: Toxicon - Volume 120, 15 September 2016, Pages 57–60