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P2X Receptor Activation

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Protein Reviews

Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 1051))

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Abstract

Extracellular ATP-gated P2X receptors are trimeric non-selective cation channels important for many physiological events including immune response and neural transmission. These receptors belong to a unique class of ligand-gated ion channels composed of only six transmembrane helices and a relatively small extracellular domain that harbors three ATP-binding pockets. The crystal structures of P2X receptors, including the recent P2X3 structures representing three different stages of the gating cycle, have provided a compelling structural foundation for understanding how this class of ligand-gated ion channels function. These structures, in combination with numerous functional studies ranging from classic mutagenesis and electrophysiology to modern optogenetic pharmacology, have uncovered unique molecular mechanisms of P2X receptor function. This review article summarizes the current knowledge in P2X receptor activation, especially focusing on the mechanisms underlying ATP-binding, conformational changes in the extracellular domain, and channel gating and desensitization.

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Abbreviations

ADP:

adenosine diphosphate

AMP:

adenosine monophosphate

ATP:

adenosine triphosphate

ATPγS:

Adenosine-5′-(γ-thio)-triphosphate

DF:

dorsal fin

hP2X2:

human P2X2 receptor

hP2X4:

human P2X4 receptor

LB:

lower body

LF:

left flipper

MTS:

methanethiosulfonate

RF:

right flipper

rP2X2:

rat P2X2 receptor

rP2X4:

rat P2X4 receptor

SCAM:

substituted cysteine accessibility method

TM:

transmembrane

UB:

upper body

VCF:

voltage clamp fluorometry

zfP2X4:

zebrafish P2X4 receptor

α,β-meATP:

(α,β-methylene)adenosine 5′-triphosphate

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Acknowledgement

I thank Kevin Michalski, Phillip Nguyen, and Akira Karasawa for helpful discussions. I am also grateful to Cindy Westmiller for helpful comments on the article. T.K. is supported by the National Institutes of Health (GM114379).

Conflicts of Interest

The author declares that I have no conflicts of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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  1. Department of Molecular Medicine, Cornell University, Ithaca, NY, 14853, USA

    Toshimitsu Kawate

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  1. Toshimitsu Kawate
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Correspondence to Toshimitsu Kawate .

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  1. Biochem and Mol Biol, Baylor College of Medicine, Houston, Texas, USA

    M. Zouhair Atassi

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© 2017 Springer Nature Singapore Pte Ltd.

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Kawate, T. (2017). P2X Receptor Activation. In: Atassi, M. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 1051. Springer, Singapore. https://doi.org/10.1007/5584_2017_55

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