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The voltage-sensitive sodium channel is a bell-shaped molecule with several cavities

Naturevolume 409, pages1047–1051 (2001)Cite this article

Abstract

Voltage-sensitive membrane channels, the sodium channel, the potassium channel and the calcium channel operate together to amplify, transmit and generate electric pulses in higher forms of life. Sodium and calcium channels are involved in cell excitation, neuronal transmission, muscle contraction and many functions that relate directly to human diseases1,2,3,4. Sodium channels—glycosylated proteins with a relative molecular mass of about 300,000 (ref.5)—are responsible for signal transduction and amplification, and are chief targets of anaesthetic drugs6 and neurotoxins1. Here we present the three-dimensional structure of the voltage-sensitive sodium channel from the eelElectrophorus electricus. The 19 Å structure was determined by helium-cooled cryo-electron microscopy and single-particle image analysis of the solubilized sodium channel. The channel has a bell-shaped outer surface of 135 Å in height and 100 Å in side length at the square-shaped bottom, and a spherical top with a diameter of 65 Å. Several inner cavities are connected to four small holes and eight orifices close to the extracellular and cytoplasmic membrane surfaces. Homologous voltage-sensitive calcium and tetrameric potassium channels, which regulate secretory processes and the membrane potential7, may possess a related structure.

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Figure 1: Cryo-electron microscopy of the sodium channel.
Figure 2: Surface representation of the sodium channel protein.
Figure 3: Domains and internal cavities of the sodium channel protein and the sequence-based structure prediction.
Figure 4: Electron microscopy of negatively stained sodium channel protein, anti-C-terminal antibody complexes and their average projections.

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Acknowledgements

We thank S. Müller for her illuminating suggestions and help with the manuscript, and M. van Heel, M. Schatz and R. Schmidt for their helpful and constructive advice. T. Moriya promoted the present research. We also thank K. Imoto for discussions, A. Oshima for suggestions and S. Miyazaki for assistance. This work was supported by grants from the ETL, the Japan New Energy and Industrial Technology Development Organization (NEDO), and the Swiss National Science Foundation (to A.E.), and by the Maurice E. Müller Foundation, Switzerland.

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Authors and Affiliations

  1. Supermolecular Science Division, Electrotechnical Laboratory (ETL), Umezono 1-1-4, Tsukuba, 305-8568, Japan

    Chikara Sato, Yutaka Ueno & Kiyoshi Asai

  2. School of Knowledge Science, Japan Advanced Institute of Science and Technology Hokuriku (JAIST), Asahidai 1-1, Tatsunokuchi, Ishikawa, 923-1211, Japan

    Katsutoshi Takahashi

  3. Central Research Institute, Itoham Foods Inc., Kubogaoka 1-2, Moriya, 302-0104, Japan

    Masahiko Sato

  4. Maurice E. Müller Institute, at the Biozentrum, University of Basel, Klingelbergstrasse 70, Basel, CH-4056, Switzerland

    Andreas Engel

  5. Department of Biophysics, Faculty of Science, Kyoto University, Oiwake, Kitashirakawa, Sakyo-ku, Kyoto, 606-8502, Japan

    Yoshinori Fujiyoshi

Authors
  1. Chikara Sato

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  2. Yutaka Ueno

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  7. Yoshinori Fujiyoshi

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Correspondence toChikara Sato.

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Sato, C., Ueno, Y., Asai, K.et al. The voltage-sensitive sodium channel is a bell-shaped molecule with several cavities.Nature409, 1047–1051 (2001). https://doi.org/10.1038/35059098

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