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The activation mechanism of alpha 1 homomeric glycine receptors

Beato, M; Groot-Kormelink, PJ; Colquhoun, D; Sivilotti, LG; (2004) The activation mechanism of alpha 1 homomeric glycine receptors. J NEUROSCI , 24 (4) 895 - 906. 10.1523/JNEUROSCI.4420-03.2004. Green open access

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Abstract

The glycine receptor mediates fast synaptic inhibition in the spinal cord and brainstem. Its activation mechanism is not known, despite the physiological importance of this receptor and the fact that it can serve as a prototype for other homopentameric channels. We analyzed single-channel recordings from rat recombinant alpha1 glycine receptors by fitting different mechanisms simultaneously to sets of sequences of openings at four glycine concentrations (10-1000 muM). The adequacy of the mechanism and the rate constants thus fitted was judged by examining how well these described the observed dwell-time distributions, open-shut correlation, and single-channel P-open dose-response curve. We found that gating efficacy increased as more glycine molecules bind to the channel, but maximum efficacy was reached when only three (of five) potential binding sites are occupied. Successive binding steps are not identical, implying that binding sites can interact while the channel is shut. These interactions can be interpreted in the light of the topology of the binding sites within a homopentamer.

Type: Article
Title: The activation mechanism of alpha 1 homomeric glycine receptors
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.4420-03.2004
Keywords: binding, channel, dose-response, gating, glycine, kinetics, patch clamp, SINGLE CHANNEL RECORD, APPARENT OPEN TIMES, ACETYLCHOLINE-RECEPTORS, SHUT TIMES, END-PLATE, ION CHANNELS, BRIEF EVENTS, AGONIST, CURRENTS, DISTRIBUTIONS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/9485
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