GlyR a1 | Glycine Receptor Alpha 1
Family:
Glycine receptors (cys-loop receptors)
Subgroups:
There are presently four known isoforms of the α-subunit (α1-4) of GlyR that are essential to bind ligands (GLRA1, GLRA2, GLRA3, GLRA4) and a single β-subunit (GLRB).
Topology:
As typical cys-loop receptors, glycine receptor subunits contain four transmembrane spanning domains TM1-TM4. Five subunits form a pore, homomeric and heteromeric combinations are possible.
Data and Applications
Glycine Receptor (GlyRa1) - Reproducible Current Recordings
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Glycine-mediated current traces and corresponding time plots from 384 simultaneously recorded HEK cells are shown. Multiple additions of 50 µM Glycine produce very robust current responses with similar peaks, providing best conditions for cumulative pharmacology on one cell.
Glycine Receptor (GlyRa1) - Pharmacology
Port-a-Patch data and applications:
Cells were kindly provided by AstraZeneca, Sweden.
The Laminar Flow Chamber can also be used for studying glycine receptors. The pharmacology of the hGlyRα1, expressed in a mouse fibroblast cell line (L-tk), was investigated. The EC50 for glycine was determined as 89 ± 2.7 μM (n = 10) which is in accordance with the literature.
Glycine Receptor (GlyRa1) - Antagonist
Patchliner data and applications:
Cells were kindly provided by Astrazeneca, Södertälje, Sweden.
The figure shows current responses of a hGlyRα1 expressing L-tk cell to alternating exposures to 100 μM glycine and 100 μM glycine + 1 μM strychnine.
Glycine Receptor (GlyRa1) - Accurate Pharmacology
Patchliner data and applications:
Cells were kindly provided by AstraZeneca.
Two different application protocols were used to study the effect of exposure time on glycine receptor pharmacology for cells expressing hGlyRα1. As shown from the raw data traces and corresponding Hill plots, the highest concentration, 3 mM glycine, did not elicit the maximum peak response during long exposures (22 s), in contrast to stacked applications (1 s).
Glycine Receptor (GlyRa1 & GlyRa3) - Dose Response Analysis
Patchliner data and applications:
(A) Effects of indicated concentrations of 3 on α1 and α3 GlyR currents activated by EC20 glycine concentrations as indicated. Unfilled bars denote glycine applications and filled bars denote compound applications. (B & C) Average dose response curves of 3 at α1 and α3 GlyRs, respectively.
Data are taken from Balansa W. et al., Bioorg Med Chem. 2010 Apr 15;18(8):2912-9.
Glycine Receptor - Potentiation
Patchliner data and applications:
Cells and the positive modulator were kindly provided by Astrazeneca, Södertälje, Sweden.
Original traces of one application of 20 μM glycine followed by 6 applications of 20 μM glycine in conjunction with increasing concentrations of a positive modulator. 1 mM glycine was used as a second positive control.
GABAA receptors - Investigation of Modulators
Patchliner data and applications:
Cells were kindly provided by AstraZeneca.
The top images show dose dependent block of GABAA currents by bicuculline. The IC50 was determined as 1.2 ± 0.2 μM (n=11). The lower graph shows the positive modulation of glycine activation of hGlyRα1. Here, six co-applications of 20 μM glycine and increasing concentrations of a positive modulator are shown.
Application Notes
Glycine receptors (GlyRa1) - "Modulators for glycine receptors investigated using the Patchliner "
Patchliner application note: 
(0.4 MB)
Cells were kindly provided by AstraZeneca.
Publications
2010 - Ircinialactams: subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae
Patchliner publication in Bioorganic & Medical Chemistry (2010)
Authors:
Balansa W, Islam R, Fontaine F, Piggott AM, Zhang H, Webb TI, Gilbert DF, Lynch JW, Capon RJ.
2009 - Port-a-Patch and Patchliner: High fidelity electrophysiology for secondary screening and safety pharmacology
Port-a-Patch and Patchliner publication in Combinatorial Chemistry & High Throughput Screening (2009)
Authors:
Farre C., Haythornthwaite A., Haarmann C., Stoelzle S., Kreir M., George M., Brüggemann A., Fertig N.
2009 - High throughput techniques for discovering new glycine receptor modulators and their binding sites
Patchliner publication in Frontiers in Molecular Neuroscience (2009)
Authors:
Gilbert D.F.,Islam R., Lynagh T., Lynch J.W., Webb T.I. Front.
2007 - Automated ion channel screening: patch clamping made easy
Port-a-Patch and Patchliner publication in Expert Opinion Therapeutic Targets (2007)
Authors:
Farre C., Stoelzle S., Haarman C., George M., Brueggemann A., Fertig N.