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Inverse coupling in leak and voltage-activated K+ channel gates underlies distinct roles in electrical signaling

Nature Structural & Molecular Biology volume 16, pages 7179 (2009) | Download Citation

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Abstract

Voltage-activated (Kv) and leak (K2P) K+ channels have key, yet distinct, roles in electrical signaling in the nervous system. Here we examine how differences in the operation of the activation and slow inactivation pore gates of Kv and K2P channels underlie their unique roles in electrical signaling. We report that (i) leak K+ channels possess a lower activation gate, (ii) the activation gate is an important determinant controlling the conformational stability of the K+ channel pore, (iii) the lower activation and upper slow inactivation gates of leak channels cross-talk and (iv) unlike Kv channels, where the two gates are negatively coupled, these two gates are positively coupled in K2P channels. Our results demonstrate how basic thermodynamic properties of the K+ channel pore, particularly conformational stability and coupling between gates, underlie the specialized roles of Kv and K2P channel families in electrical signaling.

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Acknowledgements

We thank C. Deutsch for valuable comments and insight on this manuscript. O.Y. is the incumbent of the Belle and Murray Nathan Career Development Chair in Neurobiology. N.Z. is the incumbent of the Murray and Judith Shusterman Career Development Chair in Microbiology. This research was funded by grants from the Bi-national (US-Israel) Science Foundation (BSF) to O.Y., Y.Z and N.Z. (grant 2005112) and the Israel Science Foundation (ISF) grant to N.Z. (grant 431/03).

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Affiliations

  1. Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105, Israel.

    • Yuval Ben-Abu
    • , Noam Zilberberg
    •  & Ofer Yifrach
  2. Department of Cellular and Molecular Physiology, Yale University School of Medicine, P.O. Box 208084, New Haven, Connecticut 06520-8084, USA.

    • Yufeng Zhou

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Contributions

O.Y. and N.Z. designed the research; Y.B. performed the research; O.Y., N.Z. and Y.B. analyzed the data, Y.Z contributed new insights/analytical tools and O.Y. wrote the paper.

Corresponding authors

Correspondence to Noam Zilberberg or Ofer Yifrach.

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https://doi.org/10.1038/nsmb.1525

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