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Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds

Nature Neuroscience volume 2, pages 322–330 (1999)Cite this article

Abstract

Fast synaptic transmission depends on the selective ionic permeability of transmitter-gated ion channels. Here we show changes in the ion selectivity of neuronal P2X transmitter-gated cation channels as a function of time (on the order of seconds) and previous ATP exposure. Heterologously expressed P2X2, P2X2/P2X3 and P2X4 channels as well as native neuronal P2X channels possess various combinations of mono- or biphasic responses and permeability changes, measured by NMDG+ and fluorescent dye. Furthermore, in P2X4 receptors, this ability to alter ion selectivity can be increased or decreased by altering an amino-acid residue thought to line the ion permeation pathway, identifying a region that governs this activity-dependent change.

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Figure 1: Activity-dependent increase in brain P2X4, but not P2X2 or P2X3 channel currents.
Figure 2: Properties of I1 and I2.
Figure 3: Activity-dependent increases in cation permeability of P2X4 channels.
Figure 4: Activation of neuronal P2X2 and P2X4 channels evokes YO-PRO-1 uptake.
Figure 5: ATP-evoked YO-PRO-1 uptake into neurons.
Figure 6: Mutant P2X4 channels.
Figure 7: Channel-gate mutations increase or decrease I2 amplitude.
Figure 8: Channel-gate mutants of P2X4 have high and low cation selectivity.

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Acknowledgements

Thanks to I. Chessell (GlaxoWellcome, UK) for providing P2X cDNA clones. The authors are grateful to H. Li, S. McKinney and J. Sydes for assistance with preparation of oocytes and neurons and for advice on the YO-PRO-1 experiments, and to other members of the group for comments. This work was supported by the National Institutes of Health (NS-11756), a Wellcome Trust (UK) Prize Travelling Fellowship to B.S.K. and a Caltech Summer Undergraduate Research Fellowship to X.R.B.

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  1. Division of Biology 156-29, California Institute of Technology, Pasadena, 91125, California, USA

    Baljit S. Khakh, Xiaoyan R. Bao, Cesar Labarca & Henry A. Lester

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Correspondence to Baljit S. Khakh.

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Khakh, B., Bao, X., Labarca, C. et al. Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds. Nat Neurosci 2, 322–330 (1999). https://doi.org/10.1038/7233

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