High and low GABA sensitivity α4β2δ GABAA receptors are expressed in Xenopus laevis oocytes with divergent stoichiometries

Biochemical Pharmacology
Leonny Y HartiadiNathan Absalom

Abstract

GABAA receptors that contain the α4 and δ subunits are thought to be located extrasynaptically, mediating tonic currents elicited by low concentrations of GABA. These α4βδ receptors are modulated by neurosteroids and certain anesthetics, identifying them as important drug targets in research. However, pharmacological studies on these receptors have often yielded variable results, possibly due to the expression of receptors in different stoichiometries or arrangements. In this study, we injected different ratios of α4, β2 and δ cRNA into Xenopus oocytes and measured the sensitivity to GABA and DS2 activation of the resulting receptor populations. By creating a matrix of RNA injection ratios from stock RNA concentrations, we were able to compare the changes in pharmacology between injection ratios where the ratio of only one subunit was altered. We identified two distinct populations of receptors, the first with an EC50 value of approximately 100 nM to GABA, a low Hill slope of approximately 0.3 and substantial direct activation by DS2. The second population had an EC50 value of approximately 1 μM to GABA, a steeper Hill slope of 1 and little direct activation, but substantial potentiation, by DS2. The second population was forme...Continue Reading

References

Jul 24, 2001·The Journal of Biological Chemistry·S W BaumannE Sigel
Nov 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·M WallnerR W Olsen
Jan 15, 2009·The Journal of Biological Chemistry·Kuldeep H KaurErwin Sigel
May 8, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Diego RayesCecilia Bouzat
Oct 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Delia BelelliDavid W Cope
Jul 29, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kasper HarpsøeThomas Balle
Jul 29, 2011·Journal of Neurophysiology·Pratap MeeraThomas S Otis
Sep 29, 2011·British Journal of Pharmacology·Hong-Jin ShuSteven Mennerick
Oct 6, 2012·The Journal of Biological Chemistry·Erwin Sigel, Michael E Steinmann
Nov 10, 2013·British Journal of Pharmacology·H-J FengS A Forman
Nov 12, 2013·British Journal of Pharmacology·B PatelT G Smart
Aug 17, 2014·Neuropharmacology·Paul D WhissellBeverley A Orser
Dec 5, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kirsten Hoestgaard-JensenAnders A Jensen
Feb 26, 2015·Proceedings of the National Academy of Sciences of the United States of America·Michael T BowenIain S McGregor

❮ Previous
Next ❯

Citations

Mar 17, 2017·Basic & Clinical Pharmacology & Toxicology·Christina B Falk-PetersenPetrine Wellendorph
Jun 10, 2017·Chemistry : a European Journal·Mohd Abdul Fatah Abdul MananDavid O'Hagan
Nov 7, 2019·Scientific Reports·Spencer R PierceGustav Akk
Apr 17, 2019·The Journal of General Physiology·Vivian Wan Yu LiaoPhilip Kiær Ahring
Nov 9, 2016·The Journal of Biological Chemistry·David C ChiaraJonathan B Cohen
Jan 26, 2021·British Journal of Pharmacology·Vivian Wan Yu LiaoPhilip Kiaer Ahring

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.