GABA Receptors

AND NEURONAL EXCITABILITY

GABA (ɣ-amino buytyric acid) is the primary inhibitory neurotransmitter in the central nervous system. GABA receptors belong to a family of ligand gated ion channels mediating fast synaptic transmission. They are of major importance as pharmacological targets for anxiolytics (e.g. benzodiazepines), schizophrenia, and sleep aids. At least nineteen different individual GABA A receptor subunits assemble into pentameric structures in different combinations to form the native receptor ( α1-6, β1-3, ɣ1-3, δ, ρ1-3, plus minor subunits). When activated, these receptor/channels conduct a Cl- current that desensitizes at higher GABA concentrations, with a characteristic rate for different subunit combinations. Receptors containing α1-5 subunits, any β subunits, and the ɣ2 subunit are the most prevalent in the brain. These receptors are sensitive to benzodiazepine modulation. The search for subtype-selective drugs for GABA A channels has been hampered by the lack of suitable high throughput electrophysiology platforms with the ability to interrogate ligand gated channels.

IonFlux Mercury is well established in GABA A screening facilities. Features include:

  • Continuous flow of solutions prolongs the length and stability of recordings

  • In-plate exchange of solution enables parallel and fast exchange of solutions

  • No dependence on intra-assay liquid handling; eliminates pipetting noise and enables solution exchange during recording

Application Notes

Publications & Posters

Cell Line Receptor
HEK α1/β2/δ/2
HEK α1/β3/δ/2
HEK α2/β3/δ/2
HEK α3/β3/δ/2
HEK α4/β3/δ/2
HEK α5/β3/δ/2
HEK α6/β3/δ/2
PRIMARY CELLS ENDOGENOUS
iPSC (STEM CELLS) ENDOGENOUS
Inward Cl- current from one ensemble of cells exposed to GABA with increasing concentrations (1μM to 100μM)

Inward Cl- current from one ensemble of cells exposed to GABA with increasing concentrations (1μM to 100μM)

Rapid change of solutions during GABA current activation sweeps.

Rapid change of solutions during GABA current activation sweeps.

Plate-to plate consistency in current intensity: IonFlux data showing the magnitude of the stimulus response (10 μM GABA application) for 128 cell ensembles across 8 plates, and comparison to a negative control (1% DMSO application). Z’ values (DMSO vehicle vs. 10 μM GABA) of 8 plates were 0.66, 0.45, 0.71, 0.83, 0.58, 0.72, 0.55, and 0.44. Average Z’ = 0.58±0.15.

Plate-to plate consistency in current intensity: IonFlux data showing the magnitude of the stimulus response (10 μM GABA application) for 128 cell ensembles across 8 plates, and comparison to a negative control (1% DMSO application). Z’ values (DMSO vehicle vs. 10 μM GABA) of 8 plates were 0.66, 0.45, 0.71, 0.83, 0.58, 0.72, 0.55, and 0.44. Average Z’ = 0.58±0.15.