State-dependent access to the batrachotoxin receptor on the sodium channel
State-dependent access to the batrachotoxin receptor on the sodium channel
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DOI：
10.1097/01.wnr.0000077552.91466.08
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发表时间：
2003-07-18
期刊：
影响因子：
1.7
通讯作者：
Ragsdale, DS
中科院分区：
文献类型：
--
作者：
De Leon, L;Ragsdale, DS
蝙蝠毒素导致电压门控钠通道持续打开。毒素不可逆地与野生型通道结合；然而，它在跨膜段IVS6中与突变F1710C的通道迅速分离。这种解离需要通道激活，这表明激活门保护着毒素结合位点。在这里，我们证明了活性依赖性毒素的解离不受外部钠的影响，反对孔内的结合位点，并证明解离只发生在膜去极化后的最初几毫秒，就好像毒素在激活途径的最终开放状态之前的封闭状态下离开其结合位点。毒素与预打开状态的相互作用可能促进随后的通道打开，从而解释了batrachotoxin诱导的通道激活的负移。
Batrachotoxin causes sustained opening of voltage-gated sodium channels. Toxin binds irreversibly to wild type channels; however, it dissociates rapidly from channels with mutation F1710C in transmembrane segment IVS6. This dissociation requires channel activation, suggesting that the activation gate guards the toxin-binding site. Here we show that activity-dependent toxin dissociation was not affected by external sodium, arguing against a binding site within the pore, and demonstrate that dissociation occurred only during the first few milliseconds after membrane depolarization, as if the toxin leaves its binding site during closed states that precede the final open state in the activation pathway. Toxin interaction with preopen states may facilitate subsequent channel opening, thus accounting for the batrachotoxin-induced negative shift in channel activation.