Pore dilation of neuronal P2X receptor channels.
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.
Virginio
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Geneva Biomedical Research Institute, Glaxo Wellcome, Switzerland.
MacKenzie
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A
Rassendren
F A
FA
North
R A
RA
Surprenant
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A
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D019943:Amino Acid Substitution; D000818:Animals; D001583:Benzoxazoles; D002460:Cell Line; D002463:Cell Membrane Permeability; D018076:DNA, Complementary / Q000235:genetics; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D008536:Meglumine / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009620:Nodose Ganglion / Q000166:cytology; D018408:Patch-Clamp Techniques; D017354:Point Mutation; D011806:Quinolinium Compounds; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D058476:Receptors, Purinergic P2X2; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D044406:Receptors, Serotonin, 5-HT3; D015290:Second Messenger Systems; D012701:Serotonin / Q000494:pharmacology; D014162:Transfection
D001583:Benzoxazoles; D018076:DNA, Complementary; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; C546401:P2RX2 protein, human; C548226:P2RX4 protein, human; C546468:P2RX7 protein, human; C546402:P2rx2 protein, mouse; C548227:P2rx4 protein, mouse; C546469:P2rx7 protein, mouse; D011806:Quinolinium Compounds; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; C089813:YO-PRO 1; D012701:Serotonin; D008536:Meglumine; D000255:Adenosine Triphosphate