Details

Autor(en) / Beteiligte

• Marabelli, Alessandro
• Moroni, Mirko
• Lape, Remigijus
• Sivilotti, Lucia G

Titel

The kinetic properties of the alpha 3 rat glycine receptor make it suitable for mediating fast synaptic inhibition

Ist Teil von

• The Journal of physiology, 2013-07, Vol.591 (13), p.3289-3308

Erscheinungsjahr

2013

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• times In the adult, most inhibitory transmission mediated by glycine uses channels containing alpha 1 subunits, but both alpha 1 and the related alpha 3 subunit are present in spinal areas that process pain. Abstract Glycine receptors mediate fast synaptic inhibition in spinal cord and brainstem. Two alpha subunits are present in adult neurones, alpha 1, which forms most of the synaptic glycine receptors, and alpha 3. The physiological role of alpha 3 is not known, despite the fact that alpha 3 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 alpha 3 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 alpha 3 channels resemble alpha 1 receptors in their high maximum open probability (99.1% cf. 98% for alpha 1), 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 alpha 1). alpha 3 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 alpha 3 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 alpha 3 glycine receptors, they are likely to be very close in their kinetics to alpha 1-mediated synaptic events.