Abstract
P2X receptors are ligand-gated ion channels activated by the binding of extracellular adenosine 5´-triphosphate (ATP). Brief (< 1 s) applications of ATP to nodose ganglion neurons or to cells transfected with P2X2 or P2X4 receptor cDNAs induce the opening of a channel selectively permeable to small cations within milliseconds. We now show that, during longer ATP application (10–60 s), the channel also becomes permeable to much larger cations such as N-methyl-D-glucamine and the propidium analog YO-PRO-1. This effect is enhanced in P2X2 receptors carrying point mutations in the second transmembrane segment. Progressive dilation of the ion-conducting pathway during prolonged activation reveals a mechanism by which ionotropic receptors may alter neuronal function.
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Acknowledgements
We are grateful to Daniele Estoppey and Denis Fahmi and Alison Newbolt for assistance with cell culture, transfections and mutagenesis.
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Virginio, C., MacKenzie, A., Rassendren, F. et al. Pore dilation of neuronal P2X receptor channels. Nat Neurosci 2, 315–321 (1999). https://doi.org/10.1038/7225
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DOI: https://doi.org/10.1038/7225
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