title: The kinetic properties of the α3 rat glycine receptor make it suitable for mediating fast synaptic inhibition.
abstract: Glycine receptors mediate fast synaptic inhibition in spinal cord and brainstem. Two α subunits are present in adult neurones, α1, which forms most of the synaptic glycine receptors, and α3. The physiological role of α3 is not known, despite the fact that α3 expression is concentrated in areas involved in nociceptive processing, such as the superficial dorsal horn. In the present study, we characterized the kinetic properties of rat homomeric α3 glycine receptors heterologously expressed in HEK293 cells. We analysed steady state single channel activity at a range of different glycine concentrations by fitting kinetic schemes and found that α3 channels resemble α1 receptors in their high maximum open probability (99.1% cf. 98% for α1), but differ in that maximum open probability is reached when all five binding sites are occupied by glycine (cf. three out of five sites for α1). α3 activation was best described by kinetic schemes that allow the channel to open also when partially liganded and that contain more than the minimum number of shut states, either as desensitized distal states (Jones and Westbrook scheme) or as pre-open gating intermediates (flip scheme). We recorded also synaptic-like α3 currents elicited by the rapid application of 1 ms pulses of high concentration glycine to outside-out patches. These currents had fast deactivation, with a time constant of decay of 9 ms. Thus, if native synaptic currents can be mediated by α3 glycine receptors, they are likely to be very close in their kinetics to α1-mediated synaptic events.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, Medical Sciences Building, University College London, Gower St, London WC1E 6BT, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marabelli
authors.forename: Mirko
authors.initials: M
authors.lastname: Moroni
authors.forename: Remigijus
authors.initials: R
authors.lastname: Lape
authors.forename: Lucia G
authors.initials: LG
authors.lastname: Sivilotti
mesh_terms: D000818:Animals; D001665:Binding Sites; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D051381:Rats; D018009:Receptors, Glycine / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D018009:Receptors, Glycine; C113965:glycine receptor alpha3 subunit