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The μI skeletal muscle sodium channel: Mutation E403Q eliminates sensitivity to tetrodotoxin but not to μ-conotoxins GIIIA and GIIIB

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Abstract

Voltage-sensitive Na channels from nerve and muscle are blocked by the guanidinium toxins tetrodotoxin (TTX) and saxitoxin (STX). Mutagenesis studies of brain RII channels have shown that glutamate 387 (E387) is essential for current block by these toxins. We demonstrate here that mutation of glutamate 403 (E403) of the adult skeletal muscle μI channel (corresponding to E387 of RII) also prevents current blockade by TTX and STX, and by neo-saxitoxin. However, the mutation fails to prevent blockade by the peptide neurotoxins, μ-conotoxin GIIIA and GIIIB; these toxins are thought to bind to the same or overlapping sites with TTX and STX. The E403Q mutation may have utility as a marker for exogenous Na channels in transgenic expression studies, since there are no known native channels with the same pharmacological profile.

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Author notes

  1. M. M. Stephan

    Present address: Department of Pharmacology, Yale University School of Medicine, 333 Cedar St., 06510, New Haven, Connecticut

  2. J. F. Potts & W. S. Agnew

    Present address: Department of Physiology, The Johns Hopkins School of Medicine, 725 N. Wolfe Street, 21205, Baltimore, Maryland

Authors and Affiliations

  1. Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, 06510, New Haven, Connecticut

    M. M. Stephan, J. F. Potts & W. S. Agnew

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Stephan, M.M., Potts, J.F. & Agnew, W.S. The μI skeletal muscle sodium channel: Mutation E403Q eliminates sensitivity to tetrodotoxin but not to μ-conotoxins GIIIA and GIIIB. J. Membarin Biol. 137, 1–8 (1994). https://doi.org/10.1007/BF00234993

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  • DOI: https://doi.org/10.1007/BF00234993

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