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
Recommended Reviews:
Transporter classification database:
UniProt:
- Neuronal acetylcholine receptor subunit alpha-4 (CHRNA4, Homo sapiens)
- Neuronal acetylcholine receptor subunit beta-2 (CHRNB2, Homo sapiens)
IUPHAR/PBS:
Application Notes
nAChRα4β2 - "Pharmacology of human α4β2 nAChR recorded on the SyncroPatch 384PE"
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) application note: 
(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
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
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.