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P2X receptor channels show threefold symmetry in ionic charge selectivity and unitary conductance

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Abstract

In the closed structure of the P2X cation channel, three α-helical transmembrane domains cross the membrane obliquely. In rat P2X2 receptors, these intersect at Thr339. Replacing Thr339 by lysine in one, two or three subunits progressively increased chloride permeability and reduced unitary conductance. This implies that the closed-open transition involves a symmetrical separation of the three subunits and that Thr339 from each subunit contributes symmetrically to the open channel permeation pathway.

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Figure 1: Lysine at 339 progressively increases chloride permeability and outward current.
Figure 2: Lysine at 339 reduces single channel currents.

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Acknowledgements

This work was supported by the Wellcome Trust.

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Author notes

  1. Lishuang Cao, Helen E Broomhead & William J Wilkinson

    Present address: Present addresses: Pain Research Unit, Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent, UK (L.C.), Department of Biochemistry, University of Cambridge, Cambridge, UK (H.E.B.), School of Biosciences, Cardiff University, Cardiff, UK (W.J.W.).,

  2. Liam E Browne and Lishuang Cao: These authors contributed equally to this work.

Authors and Affiliations

  1. Faculty of Medical and Human Sciences, and Faculty of Life Sciences, University of Manchester, Manchester, UK

    Liam E Browne, Lishuang Cao, Helen E Broomhead, Laricia Bragg, William J Wilkinson & R Alan North

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  1. Liam E Browne
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  2. Lishuang Cao
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  3. Helen E Broomhead
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  4. Laricia Bragg
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  6. R Alan North
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Contributions

R.A.N., L.E.B. and L.C. conceived and designed the experiments and analyzed the data. H.E.B., L.B. and W.J.W. generated the constructs and carried out western blotting. L.E.B. and L.C. performed the single-channel and whole-cell electrophysiology. L.E.B. constructed molecular models. R.A.N. wrote the paper with contributions from the other authors.

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Correspondence to R Alan North.

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The authors declare no competing financial interests.

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Supplementary Figures 1–3, Supplementary Table 1 and Supplementary Methods (PDF 1011 kb)

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Browne, L., Cao, L., Broomhead, H. et al. P2X receptor channels show threefold symmetry in ionic charge selectivity and unitary conductance. Nat Neurosci 14, 17–18 (2011). https://doi.org/10.1038/nn.2705

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  • DOI: https://doi.org/10.1038/nn.2705

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