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Functional expression of an arachnid sodium channel reveals residues responsible for tetrodotoxin resistance in invertebrate sodium channels.

Publication ,  Journal Article
Du, Y; Nomura, Y; Liu, Z; Huang, ZY; Dong, K
Published in: The Journal of biological chemistry
December 2009

Tetrodotoxin (TTX) is a potent blocker of voltage-gated sodium channels, but not all sodium channels are equally sensitive to inhibition by TTX. The molecular basis of differential TTX sensitivity of mammalian sodium channels has been largely elucidated. In contrast, our knowledge about the sensitivity of invertebrate sodium channels to TTX remains poor, in part because of limited success in functional expression of these channels. In this study, we report the functional characterization in Xenopus oocytes of the first non-insect, invertebrate voltage-gated sodium channel from the varroa mite (Varroa destructor), an ecto-parasite of the honeybee. This arachnid sodium channel activates and inactivates rapidly with half-maximal activation at -18 mV and half-maximal fast inactivation at -29 mV. Interestingly, this arachnid channel showed surprising TTX resistance. TTX blocked this channel with an IC(50) of 1 microM. Subsequent site-directed mutagenesis revealed two residues, Thr-1674 and Ser-1967, in the pore-forming region of domains III and IV, respectively, which were responsible for the observed resistance to inhibition by TTX. Furthermore, sequence comparison and additional amino acid substitutions suggested that sequence polymorphisms at these two positions could be a widespread mechanism for modulating TTX sensitivity of sodium channels in diverse invertebrates.

Duke Scholars

Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

December 2009

Volume

284

Issue

49

Start / End Page

33869 / 33875

Related Subject Headings

  • Xenopus
  • Varroidae
  • Tetrodotoxin
  • Sodium Channels
  • Sequence Homology, Amino Acid
  • Oocytes
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Models, Biological
  • Inhibitory Concentration 50
 

Citation

APA
Chicago
ICMJE
MLA
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Du, Y., Nomura, Y., Liu, Z., Huang, Z. Y., & Dong, K. (2009). Functional expression of an arachnid sodium channel reveals residues responsible for tetrodotoxin resistance in invertebrate sodium channels. The Journal of Biological Chemistry, 284(49), 33869–33875. https://doi.org/10.1074/jbc.m109.045690
Du, Yuzhe, Yoshiko Nomura, Zhiqi Liu, Zachary Y. Huang, and Ke Dong. “Functional expression of an arachnid sodium channel reveals residues responsible for tetrodotoxin resistance in invertebrate sodium channels.The Journal of Biological Chemistry 284, no. 49 (December 2009): 33869–75. https://doi.org/10.1074/jbc.m109.045690.
Du Y, Nomura Y, Liu Z, Huang ZY, Dong K. Functional expression of an arachnid sodium channel reveals residues responsible for tetrodotoxin resistance in invertebrate sodium channels. The Journal of biological chemistry. 2009 Dec;284(49):33869–75.
Du, Yuzhe, et al. “Functional expression of an arachnid sodium channel reveals residues responsible for tetrodotoxin resistance in invertebrate sodium channels.The Journal of Biological Chemistry, vol. 284, no. 49, Dec. 2009, pp. 33869–75. Epmc, doi:10.1074/jbc.m109.045690.
Du Y, Nomura Y, Liu Z, Huang ZY, Dong K. Functional expression of an arachnid sodium channel reveals residues responsible for tetrodotoxin resistance in invertebrate sodium channels. The Journal of biological chemistry. 2009 Dec;284(49):33869–33875.

Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

December 2009

Volume

284

Issue

49

Start / End Page

33869 / 33875

Related Subject Headings

  • Xenopus
  • Varroidae
  • Tetrodotoxin
  • Sodium Channels
  • Sequence Homology, Amino Acid
  • Oocytes
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Models, Biological
  • Inhibitory Concentration 50