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Page to be edited: GABAA receptor

References/Sources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243505/ (Neuroplasticity)

https://www.ncbi.nlm.nih.gov/pubmed/8783370 (Pharmacology)

https://www.ncbi.nlm.nih.gov/pubmed/16594261 (Pathophysiology)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574824/ (Alcohol binding)

https://www.ncbi.nlm.nih.gov/pubmed/22243744 (Extrasynaptic GABAa receptors)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834934/ (Depolarization)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243505/ (GABA d)

https://doi.org/10.1016/S0028-3908(01)00175-7 riluzole as a neuroprotective agent

Edit ideas for the page:

add a "3-D" cartoon picture that shows different binding sites of GABAA

add a section about the clinical significance of GABAA receptors, noting the types of drugs that are used in modern medicine that act on the channel and the physiological effects they have.

Add a section about neuroplasticity.

Delta subunit-

The δ-subunit is usually expressed in GABAA receptors associated with extrasynaptic activity. The most common GABAA subunits have the gamma subunit, which allows the receptor to bind benzodiazepines. For this reason, receptors containing δ-subunits are sometimes referred to as “benzodiazepine insensitive” GABAA receptors. The δ-subunit containing receptors are also known to be involved in the ventral tegmental area (VTA) pathway in the brain's hippocampus, which may mean that they have implications in learning, memory, and reward.[1]

Riluzole

the drug is also known to act allosterically on GABAa receptors. This action serves to postsynaptically potentiate GABAa receptor function. This action is implicated in the drug's neuroprotective qualities in its actions against ALS.[2]

Gabaa

subunits-

the section mentions the most common type of pentameric makeup, i would like to mention another.

Distribution

[edit]

GABAA receptors are responsible for most of the physiological activities of GABA in the central nervous system, but the receptor subtypes vary significantly. Subunit composition can vary widely between regions and subtypes may be associated with specific functions. The minimal requirement to produce a GABA-gated ion channel is the inclusion of an α and a β subunit.[3] The most common GABAA receptor is a pentamer comprising two α's, two β's, and a γ (α1β2γ2). In neurons themselves, the type of GABAA receptor subunits and their densities can vary between cell bodies and dendrites.[4] Interestingly, GABAA receptors can also be found in other tissues, including leydig cellsplacentaimmune cellsliverbone growth plates and several other endocrine tissues. Subunit expression varies between 'normal' tissue and malignancies and GABAA receptors can influence cell proliferation.[5]

Distribution of Receptor Types[6]
Isoform Synaptic/Extrasynaptic Anatomical location
α1β3γ2S Both Widespread
α2β3γ2S Both Widespread
α3β3γ2S Both Reticular thalamic nucleus
α4β3γ2S Both Thalamic relay cells
α5β3γ2S Both Hippocampal pyramidal cells
α6β3γ2S Both Cerebellar granule cells
α1β2γ2S Both Widespread, most abundant
α4β3δ Extrasynaptic Thalamic relay cells
α6β3δ Extrasynaptic Cerebellar granule cells
α1β2 Extrasynaptic Widespread
α1β3 Extrasynaptic Thalamus, hypothalamus
α1β2δ Extrasynaptic Hippocampus
α4β2δ Extrasynaptic Hippocampus
α3β3θ Extrasynaptic Hypothalamus
α3β3ε Extrasynaptic Hypothalamus

 

Peer Review by Caden Duffy: These sources look really good. I didn't notice any problem with them. I'll check back in a couple of days after you have written summaries on a few of them. Biophysics Editor (talk) 15:30, 26 October 2017 (UTC)
I like the idea of adding a "3-D" picture showing the binding sites of GABAa. It would really clarify for those non-scientists what it is, and how it functions. It looks like they already have some written about the clinical significance and a few examples of drugs that act on the channel. What specific types of drugs are you looking to include? -Caden
  1. ^ Oiki, S; Koeppe, R E; Andersen, O S (1995-03-14). "Voltage-dependent gating of an asymmetric gramicidin channel". Proceedings of the National Academy of Sciences of the United States of America. 92 (6): 2121–2125. ISSN 0027-8424. PMID 7534411.
  2. ^ He, Y.; Benz, A.; Fu, T.; Wang, M.; Covey, D.F.; Zorumski, C.F.; Mennerick, S. "Neuroprotective agent riluzole potentiates postsynaptic GABAA receptor function". Neuropharmacology. 42 (2): 199–209. doi:10.1016/s0028-3908(01)00175-7.
  3. ^ Connolly, Christopher N.; Krishek, Belinda J.; McDonald, Bernard J.; Smart, Trevor G.; Moss, Stephen J. (1996-01-05). "Assembly and Cell Surface Expression of Heteromeric and Homomeric -Aminobutyric Acid Type A Receptors". Journal of Biological Chemistry. 271 (1): 89–96. doi:10.1074/jbc.271.1.89. ISSN 0021-9258. PMID 8550630.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ Lorenzo, Louis-Etienne; Russier, Michaël; Barbe, Annick; Fritschy, Jean-Marc; Bras, Hélène (2007-09-10). "Differential organization of γ-aminobutyric acid type A and glycine receptors in the somatic and dendritic compartments of rat abducens motoneurons". The Journal of Comparative Neurology. 504 (2): 112–126. doi:10.1002/cne.21442. ISSN 1096-9861.
  5. ^ "GABA receptors and the immune system - OpenThesis". www.openthesis.org. Retrieved 2017-12-12.
  6. ^ Mortensen, Martin; Patel, Bijal; Smart, Trevor G. (2012). "GABA Potency at GABAA Receptors Found in Synaptic and Extrasynaptic Zones". Frontiers in Cellular Neuroscience. 6. doi:10.3389/fncel.2012.00001. ISSN 1662-5102.{{cite journal}}: CS1 maint: unflagged free DOI (link)