TABLE 3 .
Distribution of GABA-A receptor subunits in different brain regions and cell types
The GABA potency (EC50) data are obtained from recombinant HEK293 cells (Mortensen et al., 2012).
| Subunit Isoforms | Cellular Distribution | Main Brain Locations/Cell Types | GABA Potency (EC50) | Pharmacological Characterization | References |
|---|---|---|---|---|---|
| μM | |||||
| S | |||||
| α1β2γ2S | S | Ubiquitously express throughout the brain. Most abundant. Constitute ∼43%–60% of all GABA-A receptors | 6.6 | Benzodiazepines, zolpidem, and flumazenil sensitive | Sieghart (1995), McKernan and Whiting (1996), Pirker et al. (2000), Möhler et al. (2002) |
| α1β3γ2S | S | Widespread | 2.1 | Benzodiazepines and zolpidem sensitive | Sieghart (1995), Mortensen et al. (2012) |
| α2β3γ2S | S | Widespread. Account for 15%–20% of all GABA-A receptors. Hippocampal pyramidal neurons, cerebral cortex, amygdala, caudate putamen | 13.4 | Benzodiazepines, zolpidem, and flumazenil sensitive | Sieghart (1995), McKernan and Whiting (1996), Pirker et al. (2000), Möhler et al. (2002), Mortensen et al. (2012) |
| α3β3γ2S | S | Account for 10%–15% of all GABA-A receptors. Hippocampal DGGCs, hypothalamic nuclei, thalamic reticular nucleus, cerebral cortex | 12.5 | Benzodiazepines, zolpidem, and flumazenil sensitive | Sieghart (1995), Möhler et al. (2002), Mortensen et al. (2012) |
| α4β3γ2S | S | Hippocampus, thalamic relay cells | 2.1 | Furosemide and Ro15-4513 sensitive | Brown et al. (2002), Möhler et al. (2002), Mortensen et al. (2012) |
| α6β3γ2S | S | Account for ∼2% of all GABA-A receptors. Cerebellum granule cells | 0.17 | Furosemide and Ro15-4513 sensitive | McKernan and Whiting (1996), Brown et al. (2002), Möhler et al. (2002), Mortensen et al. (2012) |
| E | |||||
| α1β2δ | E | Hippocampal interneurons | 3.7 | Sun et al. (2004), Glykys et al. (2007) | |
| α3/5βδ | E | BLA principle neurons | Marowsky et al. (2004), (2012) | ||
| α3β3 | E | Thalamus, hypothalamus, locus coeruleus | 4.5 | Mortensen et al. (2012) | |
| α4β3 | E | Thalamic relay cells | 0.97 | Brickley et al. (1999), Mortensen et al. (2012) | |
| α4β2/3δ | E | Hippocampal DGGCs, thalamic relay cells, neostriatum | 0.97–1.7 | Benzodiazepines insensitive; furosemide and THIP sensitive | Sperk et al. (1997), McKernan and Whiting (1996), Brown et al. (2002), Peng et al. (2002), Farrant and Nusser (2005), Boehm et al. (2006), Mortensen et al. (2012) |
| α6β3 | E | Cerebellum granule cells | 0.076 | Mortensen et al. (2012) | |
| α6β2/3δ | E | Account for ∼2% of all GABA-A receptors. Cerebellum granule cells | 0.17 | Lacks benzodiazepine binding site; furosemide and THIP sensitive | Brown et al. (2002), Möhler et al. (2002), Boehm et al. (2006) |
| S/E | |||||
| α5β3γ2S | S/E | Account for ∼4% of all GABA-A receptors. Hippocampal pyramidal neurons, cerebral cortex, olfactory bulb | 1.4 | Benzodiazepines and flumazenil sensitive | McKernan and Whiting (1996), Möhler et al. (2002), Farrant and Nusser (2005), Mortensen et al. (2012) |
Benzodiazepines, GABA-A receptor allosteric agonists; E, extrasynaptic; flumazenil, a GABA-A receptor antagonist; furosemide, a GABA-A receptor antagonist; S, synaptic; zolpidem, a full agonist at α1-containing GABA-A receptors, ∼10-fold lower affinity at α2- and α3-containing GABA-A receptors.