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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Du, Y; Nomura, Y; Liu, Z; Huang, ZY; Dong, K

Published Date

  • December 2009

Published In

Volume / Issue

  • 284 / 49

Start / End Page

  • 33869 - 33875

PubMed ID

  • 19828457

Pubmed Central ID

  • PMC2797157

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.m109.045690

Language

  • eng