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.
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.
Marine Biotoxins Program, Environmental and Fisheries Sciences Division, Northwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, 2725 Montlake Boulevard East, Seattle, Washington 98112 United States.
Nicolaus G
NG
Adams
Department of Marine Sciences, University of South Alabama, 5871 University Boulevard North, Mobile, Alabama 36688 United States; Dauphin Island Sea Lab, 101 Bienville Boulevard, Dauphin Island, Alabama 36528 United States.
Alison
A
Robertson
Department of Neurology, University of Maryland School of Medicine, 16 South Eutaw Street, Baltimore, Maryland 21201, United States.
Lynn M
LM
Grattan
Makah Tribe, Environmental Health Division, P.O. Box 115, Neah Bay, Washington 98357, United States.
Steve
S
Pendleton
Department of Neurology, University of Maryland School of Medicine, 16 South Eutaw Street, Baltimore, Maryland 21201, United States.
Sparkle
S
Roberts
Department of Neurology, University of Maryland School of Medicine, 16 South Eutaw Street, Baltimore, Maryland 21201, United States.
J Kathleen
JK
Tracy
Marine Biotoxins Program, Environmental and Fisheries Sciences Division, Northwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, 2725 Montlake Boulevard East, Seattle, Washington 98112 United States.
Vera L
VL
Trainer
harmful algal blooms; paralytic shellfish poisoning; resistance; saxitoxin; voltage gated Na+ channel