• nAChRα4β2

    Currents elicited in response to increasing concentrations of ACh measured on the Patchliner

    Alijevic O. et al., 2020

AChRa4b2 | nicotinic acetylcholine receptor alpha 4 beta 2

Family:
Acetylcholine Receptors

Subgroups:
The family has been devided into nicotinic acetylcholine receptors (ionotropic channels) and muscarinic acetylcholine receptors (metabotropic G-protein coupled receptors). Both subgroups are sensitive to acetylcholine.

Topology:
Nicotinic acetylcholine receptors: As typical cys-loop receptors, acetylcholine receptor subunits contain four transmembrane spanning domains TM1-TM4. Five subunits form a pore, homomeric and heteromeric combinations are possible.17 vertebrate subunits have been identified: α genes: CHRNA1 - CHRNA10; β genes: CHRNB1 . CHRNB4, as well as CHRND (delta), CHRNE (epsilon), CHRNG (gamma)
Muscarinic acetylcholine receptors: 5 receptors have been described (M1 - M5), encoded by the 5 genes CHRM1 - CHRM5. These proteins contain seven transmembrane regions and do not form homo or heteromers. 

AChRα4β2: Background Information


Overview:

The alpha-4 beta-2 nicotinic receptor, also known as the α4β2 receptor, is a type of nicotinic acetylcholine receptor implicated in learning. Among the nicotinic receptor subtypes, nicotine has the highest binding affinity at the α4β2 receptor (ki=1 nM), which is also the primary biological target that mediates nicotine's addictive properties.


Data Sheet:

Gene:
CHRNA4, CHRNB2

Human Protein:
UniProt P43681, P17787

Tissue:
Brain

Function/ Application:
Its activation yields post- and presynaptic excitation, mainly by increased Na+ and K+ permeability. Stimulation of this receptor subtype is also associated with growth hormone secretion.

Pathology:
Epilepsy, nocturnal frontal lobe, 1 (ENFL1), paroxysmal kinesogenic dyskinesia

Accessory subunits:
The Alpha-4 subunit can be combined to beta-2 or beta-4 to give rise to functional receptors, complexes with beta-2 may be heteropentamers

Interaction:
RIC3, LYPD6, the heteropentamer alpha-4-beta-2 interacts with alpha-conotoxins PnIA, GID and MII

Modulator:
Nicotine, acetylcholine, α-Conotoxin, Isoflurane

Assays:
Patch Clamp: whole cell, room temperature

Reviews and Links

Application Notes

nAChRα4β2 - "Pharmacology of human α4β2 nAChR recorded on the SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) application note:   logo pdf   (0.8 MB)
Cells were engineered and kindly provided by SB Drug Discovery.  

Publications

2020 - An electrophysiological characterization of naturally occurring tobacco alkaloids and their action on human α4β2 and α7 nicotinic acetylcholine receptors

icon pl   Patchliner publication in Phytochemistry (2020)

Authors:
Alijevic O., McHugh D., Rufener L., Mazurov A., Hoeng J., Peitsch M.

2020 - Discovery and Development of SUVN-911: A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine α4β2 Receptor Antagonist for the Treatment of Depression

icon pl  Patchliner publication in Journal of Medicinal Chemistry (2020)

Authors:
Nirogi R., Mohammed A.R., Shinde A.K., Ravella S.R., Bogaraju N., Subramanian R., Mekala V.R., Palacharla R.C., Muddana N., Thentu J.B., Bhyrapuneni G., Abraham R., Jasti V.

 

 

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.