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Gating the pore of P2X receptor channels

Nature Neuroscience volume 11, pages 883–887 (2008)Cite this article

Abstract

Three families of ligand-activated ion channels mediate synaptic communication between excitable cells in mammals. For pentameric channels related to nicotinic acetylcholine receptors and tetrameric channels such as glutamate receptors, the pore-forming and gate regions have been studied extensively. In contrast, little is known about the structure of trimeric P2X receptor channels, a family of channels that are activated by ATP and are important in neuronal signaling, pain transmission and inflammation. To identify the pore-forming and gate regions in P2X receptor channels, we introduced cysteine residues throughout the two transmembrane (TM) segments and studied their accessibility to thiol-reactive compounds and ions. Our results show that TM2 lines the central ion-conduction pore, TM1 is positioned peripheral to TM2 and the flow of ions is minimized in the closed state by a gate formed by the external region of TM2.

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Figure 1: Transmembrane segments in P2X receptor channels.
Figure 2: State-dependent accessibility of extracellular MTSET in P2X2 receptor channels.
Figure 3: State-dependent accessibility of extracellular Ag+ in P2X2 receptor channels.
Figure 4: Stable coordination of Cd2+ at T336C.
Figure 5: Architecture of the pore of P2X receptor channels.

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Acknowledgements

We thank J. Contreras and M. Holmgren for extensive advice in using the thiol-reactive compounds described in this study. We also thank M. Holmgren, J. Mindell and members of the Swartz lab for helpful discussions, and the US National Institute of Neurological Disorders and Stroke DNA sequencing facility for DNA sequencing. This work was supported by the Intramural Research Program of the US National Institute of Neurological Disorders and Stroke.

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  1. Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, US National Institute of Neurological Disorders and Stroke, US National Institutes of Health, 35 Convent Drive, MSC 3701, Bethesda, 20892, Maryland, USA

    Mufeng Li, Tsg-Hui Chang, Shai D Silberberg & Kenton J Swartz

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  1. Mufeng Li
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Correspondence to Shai D Silberberg or Kenton J Swartz.

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Li, M., Chang, TH., Silberberg, S. et al. Gating the pore of P2X receptor channels. Nat Neurosci 11, 883–887 (2008). https://doi.org/10.1038/nn.2151

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