Anti-Nicotinic Acetylcholine Receptor α3 (CHRNA3) (extracellular) Antibody

Acetylcholine, released by cholinergic neurons, activates two groups of acetylcholine receptors (AChRs); muscarinic AChRs (mAChRs) which belong to the superfamily of G-protein coupled receptors (GPCRs) and nicotinic AChRs (nAChRs) which belong to the ligand-gated ion channel superfamily. nAChRs also respond to nicotine, hence their name¹.

To date, 17 different but related subunits of nAChRs have been identified and cloned. They consist of a subunits (α1-10), which is responsible for the binding of ligands. In fact, this subunit includes a Cys-loop in the first extracellular domain that is required for agonist binding². The other subunits responsible for making up the active receptor are the β (β1-4), γ, δ and ε subunits³. Structurally, all subunits have the following: a conserved large extracellular N-terminal domain, 3 conserved transmembrane domains, a variable cytoplasmic loop and a fourth transmembrane domain with a short extracellular C-terminal domain.  An active nAChR is generally a heteropentamer of these various subunits organized around a central pore¹.

All α subunits are expressed in neuronal cells except for the α1 subunit which is specifically expressed in the muscle³. In the peripheral autonomic nervous system, nicotinic receptors are prominent and are responsible mediating fast synaptic transmission in all peripheral autonomic ganglia⁴. In this system, these channel receptors are mostly made up of two α3 subunits heteromerized with three other subunits. The α3 subunit plays a most important role in this system as knockout mice suffer from severe autonomic failure accompanied by gastrointestinal and bladder malfunctions⁵.

Autoimmune autonomic ganglionopathy (AAG) is a neurological disorder characterized by dysfunctions in sympathetic, parasympathetic and enteric functions. Patients suffering from the disease express high levels of self antibodies against ionotropic nicotinic receptors, namely α3 subunits⁴. The α3 subunit is also found in dorsal root ganglion where it is most probably involved in nociception⁶.