AChR

AChR, or acetylcholine receptor, denotes receptors that respond to the neurotransmitter acetylcholine. The two major families are nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels, and muscarinic acetylcholine receptors (mAChRs), which are G protein-coupled receptors. AChRs are widely distributed in the peripheral and central nervous systems and at the neuromuscular junction.

Nicotinic acetylcholine receptors are pentameric ion channels. Muscle-type nAChRs are typically composed of subunits arranged as (α1)2β1δε, while neuronal nAChRs have various subunit combinations. Binding of acetylcholine opens the channel, allowing sodium influx and potassium efflux, producing rapid depolarization and excitation. They are abundant at the neuromuscular junction and also present in certain brain regions and autonomic ganglia.

Muscarinic acetylcholine receptors consist of five subtypes, M1 through M5, and function as G protein-coupled receptors. Each subtype couples to different G proteins to influence signaling pathways such as cAMP, phospholipase C, and intracellular calcium. M2 receptors in the heart typically slow heart rate, while M3 receptors mediate glandular secretion and smooth muscle contraction. M1 and other subtypes contribute to neural signaling and cognitive processes. These receptors are widely expressed in the brain, heart, smooth muscle, and exocrine tissues.

Clinical relevance and pharmacology: autoimmune myasthenia gravis involves antibodies against AChR at the neuromuscular junction, reducing transmission; Lambert-Eaton myasthenic syndrome involves impaired presynaptic acetylcholine release. Pharmacologic agents include agonists such as nicotine (nAChR) and muscarine (mAChR), and antagonists such as curare-like compounds (nAChR blockers) and atropine or scopolamine (mAChR antagonists). Acetylcholinesterase inhibitors increase acetylcholine levels to enhance transmission in MG. AChR function is a focus of neuropharmacology and disease research.