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Nat Neurosci. 2008 Aug;11(8):883-7. doi: 10.1038/nn.2151. Epub 2008 Jun 29.

Gating the pore of P2X receptor channels.

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Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, US National Institute of Neurological Disorders and Stroke, US National Institutes of Health, 35 Convent Drive, MSC 3701, Bethesda, Maryland 20892, USA.


Three families of ligand-activated ion channels mediate synaptic communication between excitable cells in mammals. For pentameric channels related to nicotinic acetylcholine receptors and tetrameric channels such as glutamate receptors, the pore-forming and gate regions have been studied extensively. In contrast, little is known about the structure of trimeric P2X receptor channels, a family of channels that are activated by ATP and are important in neuronal signaling, pain transmission and inflammation. To identify the pore-forming and gate regions in P2X receptor channels, we introduced cysteine residues throughout the two transmembrane (TM) segments and studied their accessibility to thiol-reactive compounds and ions. Our results show that TM2 lines the central ion-conduction pore, TM1 is positioned peripheral to TM2 and the flow of ions is minimized in the closed state by a gate formed by the external region of TM2.

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