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.
MeSH terms
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Adenosine Triphosphate / pharmacology*
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Amino Acid Substitution
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Animals
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Benzoxazoles
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Cell Line
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Cell Membrane Permeability
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DNA, Complementary / genetics
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Fluorescent Dyes / metabolism
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Humans
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Ion Transport
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Meglumine / metabolism
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Mice
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Mutagenesis, Site-Directed
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Nerve Tissue Proteins / chemistry*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nodose Ganglion / cytology
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Patch-Clamp Techniques
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Point Mutation
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Quinolinium Compounds
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Rats
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Receptors, Purinergic P2 / chemistry*
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Receptors, Purinergic P2 / genetics
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Receptors, Purinergic P2 / metabolism
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Receptors, Purinergic P2 / physiology
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Receptors, Purinergic P2X2
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Receptors, Purinergic P2X4
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Receptors, Purinergic P2X7
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Receptors, Serotonin / drug effects
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Receptors, Serotonin / genetics
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Receptors, Serotonin / physiology
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Receptors, Serotonin, 5-HT3
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Second Messenger Systems
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Serotonin / pharmacology
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Transfection
Substances
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Benzoxazoles
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DNA, Complementary
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Fluorescent Dyes
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Nerve Tissue Proteins
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P2RX2 protein, human
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P2RX4 protein, human
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P2RX7 protein, human
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P2rx2 protein, mouse
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P2rx4 protein, mouse
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P2rx7 protein, mouse
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Quinolinium Compounds
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Receptors, Purinergic P2
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Receptors, Purinergic P2X2
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Receptors, Purinergic P2X4
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Receptors, Purinergic P2X7
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Receptors, Serotonin
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Receptors, Serotonin, 5-HT3
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YO-PRO 1
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Serotonin
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Meglumine
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Adenosine Triphosphate