Assessment of sodium channel mutations in Makah tribal members of the U.S. Pacific Northwest as a potential mechanism of resistance to paralytic shellfish poisoning

Abstract

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, we 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 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.

Human Health and Ocean Pollution

“…In high-income countries, consumers’ perception of the safety of seafood has led to a reduction in demand for shellfish, and this change has had severe economic consequences for the shellfish industry [ 512 ]. The lack of diagnostic tools and treatment options for HAB-related illnesses leads to increased psychological stress in fishing communities [ 513 514 ].…”

Taking the Long View for Oceans and Human Health Connection through Community Driven Science

“…Nearly 70% of households participate in shellfish harvest activities [ 32 ]. Members of the Makah Tribe tell the story of potlatches (tribal ceremonial feasts) where visitors would come from over the mountains to share in the seafood bounty [ 32 , 33 ]. These stories suggest that the visitors became ill from consuming shellfish which contained toxins, while the Makah, who habitually rely on shellfish in their diet, did not.…”

“…These traditional stories provided inspiration to further our understanding of genetic resistance to toxins in shellfish that consume toxic algae [ 34 ], leading to a collaboration with the Makah Tribe to understand whether people, such as the Makah, who consumed shellfish also demonstrated resistance to toxins. This study showed that, in contrast to shellfish which can feed on and accumulate toxic algae and survive [ 32 , 34 ], tribal members do not appear to be resistant to toxins in their shellfish food [ 33 ]. This knowledge informed an optimal strategy for human health protection and outreach associated with HABs and their toxins.…”