AChRa3b4 | nicotinic acetylcholine receptor alpha 3 beta 4
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.
AChRα3β4: Background Information
Overview:
The alpha-3 beta-4 nicotinic receptor, also known as the α3β4 receptor and the ganglion-type nicotinic receptor, is a type of nicotinic acetylcholine receptor, consisting of α3 and β4 subunits. In the peripheral nervous system (PNS), the most abundant subtypes are α3β2* and α3β4* and are prominently expressed by ganglionic neurons. Because the α3β4 AChR subtype is predominantly expressed in nociceptive DRG neurons, it has been suggested that this subtype may be involved in neuronal signalling of nociception and inflammation.
Data Sheet:
Gene:
CHRNA3, CHRNB4
Human Protein:
UniProt P32297, P30926
Tissue:
Brain, hippocampus, cerebellum, retina. (α3β4β2) nAChRs are present on glutamate axons innervating Stratum radiatum (SR) interneurons and possibly other interneurons. PNS: The α3β4 subtype is prominently expressed in a variety of PNS neurons including those of DRG, superior cervical ganglia, cardiac ganglia, and ganglia innervating the viscera. The α3 subunit is furthermore expressed in the adrenal gland and lymphoid tissue
Function/ Application:
Mediates effects of acetylcholine and nicotine in specific regions of the brain, retina and spinal cord, post- and presynaptic excitation
Pathology:
Sporadic amyotrophic lateral sclerosis, genetic variations in CHRNA3 (Neuronal acetylcholine receptor subunit alpha-3) have been associated with susceptibility to smoking-related behavioral traits and lung cancer, nicotine dependence
Accessory subunits:
Neuronal AChR is composed of two different types of subunits: alpha and beta. Alpha-3 subunit can be combined to beta-2 or beta-4 to give rise to functional receptors (furthermore, the Alpha-3 subunit can form a neuronal nicotinic acetylcholine receptor complex with the AChR Alpha-5 subunit: Alpha-3, Alpha-5, Beta-2 or Alpha-3, Alpha-5, Beta-4)
Interaction:
RIC3, LYPD6, alpha-conotoxin ImI
Modulator:
Acetylcholine, nicotine, epibatidine, DHβE, mecamylamine, α-conotoxin, hexamethonium, A-867744, NS1738
Assays:
Patch Clamp: whole cell, room temperature
Reviews and Links
Recommended Reviews:
Transporter classification database:
UniProt:
- Neuronal acetylcholine receptor subunit alpha-3 (CHRNA3, Homo sapiens)
- Neuronal acetylcholine receptor subunit beta-4 (CHRNB4, Homo sapiens)
IUPHAR/PBS:
Data and Applications
Acetylcholine Receptor Alpha 3 Beta 4 - Concentration Response Curve to Nicotine
Patchliner data and applications:
Shown are the a raw current responses of a HEK293 cell expressing AChR (α3β4) to increasing concentrations of nicotine. Solutions were stacked (layered) in the pipette to achieve brief exposure times.
Application Notes
Acetylcholine Receptor Alpha 3 Beta 4 - " Nicotinic a3b4 receptors recorded on Nanion's Patchliner"
Patchliner application note: 
(0.5 MB)
Publications
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.