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Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP

Nature volume 434, pages 763–767 (2005)Cite this article

Abstract

Bivalve molluscs, the primary vectors of paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their capacity to accumulate PSP toxins (PSTs)1 which has a neural basis2,3. PSTs cause human fatalities by blocking sodium conductance in nerve fibres4,5. Here we identify a molecular basis for inter-population variation in PSP resistance within a species, consistent with genetic adaptation to PSTs. Softshell clams (Mya arenaria) from areas exposed to ‘red tides’ are more resistant to PSTs, as demonstrated by whole-nerve assays, and accumulate toxins at greater rates than sensitive clams from unexposed areas. PSTs lead to selective mortality of sensitive clams. Resistance is caused by natural mutation of a single amino acid residue, which causes a 1,000-fold decrease in affinity at the saxitoxin-binding site in the sodium channel pore of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans. Furthermore, global expansion of PSP to previously unaffected coastal areas6 might result in long-term changes to communities and ecosystems.

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Figure 1: Responses to PSTs in two M. arenaria populations.
Figure 2: Nerve response of toxin-free, individual clams to STX in vitro.
Figure 3: Mutation in the Na+ channel pore of resistant M. arenaria.
Figure 4: Blocking of WT and mutant Na+ channels by TTX and STX.

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Acknowledgements

We thank B. M. Twarog, whose seminal work in the 1970s inspired this study, for conducting the initial nerve tests; P. Chang for participating in the burrowing experiment; M. Quilliam and the IMB analytical toxins group for providing STX for nerve tests; and E. M. Sharp and M. Iszard for technical assistance. This work was supported by a US NOAA-ECOHAB grant to V.L.T. and V.M.B., a NOAA-ECOHAB grant to L.C., V.L.T. and V.M.B., and an NIH research grant to W.A.C.

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Authors and Affiliations

  1. Institute for Marine Biosciences, National Research Council, Halifax, Nova Scotia, B3H 3Z1, Canada

    V. Monica Bricelj & Scott P. MacQuarrie

  2. School of Marine Sciences, University of Maine, Orono, Maine, 04469, USA

    Laurie Connell

  3. Department of Pharmacology, University of Washington, Seattle, Washington, 98195, USA

    Keiichi Konoki, Todd Scheuer & William A. Catterall

  4. NOAA Fisheries, Northwest Fisheries Science Center, Seattle, Washington, 98112, USA

    Vera L. Trainer

Authors
  1. V. Monica Bricelj
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Correspondence to V. Monica Bricelj.

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Supplementary information

Supplementary Figure S1

Illustrates voltage-dependent electrophysiological properties (activation and inactivation of the Na+ current) of transfected wild-type and mutant Na+ channels. (DOC 567 kb)

Supplementary Discussion

Includes a discussion of differences in the sensitivity to toxins between Mya arenaria nerves and transfected Na+ channels, and references cited therein. (DOC 27 kb)

Supplementary Methods

Describes the methods of clam nucleic acid extraction, production of cDNA, isolation of Na+ channel specific fragments, determination of the Na+ channel sequence from individual clams, and the construction of Na+ channel mutations, including cited references. (DOC 40 kb)

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Bricelj, V., Connell, L., Konoki, K. et al. Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP. Nature 434, 763–767 (2005). https://doi.org/10.1038/nature03415

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