Nature Neuroscience
2, 315 - 321 (1999)
doi:10.1038/7225
Pore dilation of neuronal P2X receptor channelsC. Virginio2, 3, A. MacKenzie1, 2, F. A. Rassendren2, 4, R. A. North1, 2
& A. Surprenant1, 21
Institute of Molecular Physiology, University of Sheffield, Sheffield S10 2TN, England
2
Geneva Biomedical Research Institute, GlaxoWellcome , Geneva, Switzerland
3
Present address: GlaxoWellcome SPA, Via A. Fleming, 2-37100 Verona, Italy
4
Present address: Institut de Genetique Humaine, CNRS UPR 1142, 34396 Montpellier, Cedex 5, France
Correspondence should be addressed to A. Surprenant a.surprenant@sheffield.ac.ukP2X 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.
|
