Acetylcholine receptor anatomy

The acetylcholine receptor (AChR) is a membrane protein that binds to the neurotransmitter acetylcholine (Ach). These receptors can be divided into two main types of distinct receptors, nicotinic and muscarinic. Nicotinic acetylcholine receptors (nAChR) are pentameric ligand-gated ion channels, whereas muscarinic acetylcholine receptors (mAChR) are seven-helix G-protein coupled membrane proteins.

Nicotinic acetylcholine receptors (nAChR) These ligand-gated ion channels are present at the neuromuscular junction and signal muscular contraction with stimulation. The mature nicotinic acetylcholine receptor at the postsynaptic (muscular) membrane is composed of 5 subunits (two α, and one each of β, δ, and ε subunits). These subunits are arranged in a barrel or cylindrical shape around a central pore. Each of the two α subunits has an acetylcholine-binding site. The protein-receptor complex spans the entire membrane and extends from cytoplasm to beyond the extracellular membrane. Acetylcholine binds to the α subunit; both α subunits must be bound to an acetylcholine molecule in order to trigger conformational change of ion channel to allow influx of calcium and sodium ions intracellularly, and to allow efflux of potassium out of cell.

The fetal or immature receptor is also referred to as “extrajunctional” because it can be located anywhere in the muscle membrane, inside or outside the neuromuscular junction. It consists of α, β, δ, and γ subunits; there are two subunits of α and one each of the others.

The α subunit is also the site of action of acetylcholine receptor agonists and antagonists.

Finally, the ganglion type nicotinic receptor is a type of nicotinic acetylcholine receptor that is located in the autonomic ganglia.

Muscarinic acetylcholine receptors (mAChR) These receptors are seven transmembrane G-protein coupled receptors. The structure of the receptors varies between tissues and different times in development. There are five described subtypes of muscarinic receptors (M1-M5). mAChR play major role in the parasympathetic nervous system for diverse functions, including regulation of smooth muscle activity, wakefulness, hormone secretion, heart rate.