• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Oct 1989; 86(20): 8147–8151.
PMCID: PMC298232

Inhibition of inactivation of single sodium channels by a site-directed antibody.

Abstract

The effects of site-directed antibodies on single sodium channel currents in excised membrane patches from rat brain neurons have been examined. Of six antibodies directed against different intracellular domains of the sodium channel alpha subunit, only an antibody directed against a highly conserved intracellular segment between homologous transmembrane domains III and IV induced late single channel openings and prolonged single channel open times during depolarizing test pulses, resulting in nearly complete inhibition of sodium channel inactivation. The antibody effect was not observed if the membrane patches were depolarized to inactivate sodium channels before exposure to the antibody, indicating that the intracellular sequence recognized by the antibody is rendered inaccessible by inactivation. The results show that a conformational change involving the intracellular segment between domains III and IV of the alpha subunit of the sodium channel molecule is required for fast sodium channel inactivation and suggest that this segment may be the fast inactivation gate of the sodium channel.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Catterall WA. Structure and function of voltage-sensitive ion channels. Science. 1988 Oct 7;242(4875):50–61. [PubMed]
  • Noda M, Ikeda T, Kayano T, Suzuki H, Takeshima H, Kurasaki M, Takahashi H, Numa S. Existence of distinct sodium channel messenger RNAs in rat brain. Nature. 1986 Mar 13;320(6058):188–192. [PubMed]
  • Kayano T, Noda M, Flockerzi V, Takahashi H, Numa S. Primary structure of rat brain sodium channel III deduced from the cDNA sequence. FEBS Lett. 1988 Feb 8;228(1):187–194. [PubMed]
  • Goldin AL, Snutch T, Lübbert H, Dowsett A, Marshall J, Auld V, Downey W, Fritz LC, Lester HA, Dunn R, et al. Messenger RNA coding for only the alpha subunit of the rat brain Na channel is sufficient for expression of functional channels in Xenopus oocytes. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7503–7507. [PMC free article] [PubMed]
  • Noda M, Ikeda T, Suzuki H, Takeshima H, Takahashi T, Kuno M, Numa S. Expression of functional sodium channels from cloned cDNA. Nature. 322(6082):826–828. [PubMed]
  • Auld VJ, Goldin AL, Krafte DS, Marshall J, Dunn JM, Catterall WA, Lester HA, Davidson N, Dunn RJ. A rat brain Na+ channel alpha subunit with novel gating properties. Neuron. 1988 Aug;1(6):449–461. [PubMed]
  • Suzuki H, Beckh S, Kubo H, Yahagi N, Ishida H, Kayano T, Noda M, Numa S. Functional expression of cloned cDNA encoding sodium channel III. FEBS Lett. 1988 Feb 8;228(1):195–200. [PubMed]
  • Vassilev PM, Scheuer T, Catterall WA. Identification of an intracellular peptide segment involved in sodium channel inactivation. Science. 1988 Sep 23;241(4873):1658–1661. [PubMed]
  • Gordon D, Merrick D, Auld V, Dunn R, Goldin AL, Davidson N, Catterall WA. Tissue-specific expression of the RI and RII sodium channel subtypes. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8682–8686. [PMC free article] [PubMed]
  • Gordon D, Merrick D, Wollner DA, Catterall WA. Biochemical properties of sodium channels in a wide range of excitable tissues studied with site-directed antibodies. Biochemistry. 1988 Sep 6;27(18):7032–7038. [PubMed]
  • Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. [PubMed]
  • Yue DT, Lawrence JH, Marban E. Two molecular transitions influence cardiac sodium channel gating. Science. 1989 Apr 21;244(4902):349–352. [PubMed]
  • Aldrich RW, Corey DP, Stevens CF. A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature. 1983 Dec 1;306(5942):436–441. [PubMed]
  • Horn R, Vandenberg CA. Statistical properties of single sodium channels. J Gen Physiol. 1984 Oct;84(4):505–534. [PMC free article] [PubMed]
  • Gonoi T, Hille B. Gating of Na channels. Inactivation modifiers discriminate among models. J Gen Physiol. 1987 Feb;89(2):253–274. [PMC free article] [PubMed]
  • Armstrong CM. Sodium channels and gating currents. Physiol Rev. 1981 Jul;61(3):644–683. [PubMed]
  • Salgado VL, Yeh JZ, Narahashi T. Voltage-dependent removal of sodium inactivation by N-bromoacetamide and pronase. Biophys J. 1985 Apr;47(4):567–571. [PMC free article] [PubMed]
  • Stühmer W, Conti F, Suzuki H, Wang XD, Noda M, Yahagi N, Kubo H, Numa S. Structural parts involved in activation and inactivation of the sodium channel. Nature. 1989 Jun 22;339(6226):597–603. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...