Poisonous organisms carry small molecule toxins that alter voltage-gated sodium channel (NaV) function. Among these, batrachotoxin (BTX) from Pitohui toxic birds and Phyllobates poison frogs, stands out because of its lethality and unusual effects on NaV function. How these toxin-bearing organisms avoid autointoxication remains poorly understood. In poison frogs, a NaV DIVS6 pore forming helix N->T mutation has been proposed as the BTX resistance mechanism. Here, we show that this variant is absent from Pitohui and poison frog NaVs, incurs a strong cost that compromises channel function, and fails to produce BTX resistant channels when tested in the context of poison frog NaVs. We further show that captive-raised poison frogs are BTX resistant, even though they bear BTX sensitive NaVs. Hence, our data refute the hypothesis that BTX autoresistance is rooted in NaV mutations and instead suggest that more generalizable mechanisms such as toxin sequestration act to protect BTX bearing species from autointoxication.

中文翻译：

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钠通道毒素抗性突变不控制毒禽和青蛙中的梭菌毒素（BTX）自体抗性

有毒生物携带会改变电压门控钠通道（NaV）功能的小分子毒素。其中，来自Pitohui的有毒鸟类的毛状胆毒素（BTX）和Phyllobates的有毒青蛙，因其致死性和对NaV功能的异常影响而脱颖而出。这些含毒素的生物如何避免自身中毒仍然知之甚少。在毒蛙中，已提出NaV DIVS6孔形成螺旋N-> T突变作为BTX抗性机制。在这里，我们证明了Pitohui和毒蛙NaVs中不存在此变体，招致了高昂的成本，损害了通道功能，并且在毒蛙NaVs中进行测试时无法产生抗BTX的通道。我们进一步表明，圈养的毒蛙即使对BTX敏感的NaV仍能抵抗BTX。因此，