Assessment of sodium channel mutations in Makah tribal members of the US Pacific Northwest as a potential mechanism of resistance to paralytic shellfish poisoning
Assessment of sodium channel mutations in Makah tribal members of the US Pacific Northwest as a potential mechanism of resistance to paralytic shellfish poisoning
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DOI：
10.1016/j.hal.2016.03.008
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发表时间：
2016-07-01
期刊：
影响因子：
6.6
通讯作者：
Trainer, Vera L.
中科院分区：
文献类型：
--
作者：
Adams, Nicolaus G.;Robertson, Alison;Trainer, Vera L.
华盛顿州尼亚湾的马卡部落历来依赖沿海海鲜（包括贝类）的捕捞维持生计，贝类仍然是重要的文化和仪式资源。部落传说描述了来自其他部落的游客因食用在马卡土地上收集的贝类而死亡的故事。这些死亡被认为是由麻痹性贝类中毒引起的，这是一种因摄入被石房蛤毒素污染的贝类而引起的人类疾病，这种毒素是由贝类赖以生存的产毒素海洋甲藻产生的。这些麻痹性贝类毒素包括石房蛤毒素，这是一种有效的 Na+ 通道拮抗剂，可与电压门控 Na+ 通道的孔区域结合。 Na+通道孔中的氨基酸突变已被证明可以赋予暴露于环境中存在的麻痹性贝类毒素的软壳蛤种群对石房蛤毒素的抵抗力。由于对麻痹性贝类毒素具有抵抗力的概念，该研究旨在确定历史上接触过贝类毒素的人类是否可以采取抵抗策略。我们从 83 名 Makah 部落志愿者的口腔拭子中收集、提取和纯化 DNA，并对 9 个位点的骨骼肌 Na+ 通道 (Nav1.4) 进行测序，以表征相关石房蛤毒素结合区域的潜在突变。与参考序列比较后，没有发现这些特定区域的突变。这项研究表明，Makah 部落成员对石房蛤毒素的任何抵抗力（如果存在）并不是 Nav1.4 修饰的功能，但可能是由于。神经元或心脏钠通道的突变，或与钠通道功能无关的其他机制。由 Elsevier B.V. 出版
The Makah Tribe of Neah Bay, Washington, has historically relied on the subsistence harvest of coastal seafood, including shellfish, which remains an important cultural and ceremonial resource. Tribal legend describes visitors from other tribes that died from eating shellfish collected on Makah lands. These deaths were believed to be caused by paralytic shellfish poisoning, a human illness caused by ingestion of shellfish contaminated with saxitoxins, which are produced by toxin producing marine dinoflagellates on which the shellfish feed. These paralytic shellfish toxins include saxitoxin, a potent Na+ channel antagonist that binds to the pore region of voltage gated Na+ channels. Amino acid mutations in the Na+ channel pore have been demonstrated to confer resistance to saxitoxin in softshell clam populations exposed to paralytic shellfish toxins present in their environment. Because of the notion of resistance to paralytic shellfish toxins, the study aimed to determine if a resistance strategy was possible in humans with historical exposure to toxins in shellfish. We collected, extracted and purified DNA from buccal swabs of 83 volunteer Makah tribal members and sequenced the skeletal muscle Na+ channel (Nav1.4) at nine loci to characterize potential mutations in the relevant saxitoxin binding regions. No mutations of these specific regions were identified after comparison to a reference sequence. This study suggests that any resistance of Makah tribal members to saxitoxin, if present, is not a function of Nav1.4 modification, but may be due to. mutations in neuronal or cardiac sodium channels, or some other mechanism unrelated to sodium channel function. Published by Elsevier B.V.