5.6:
Cholinergic Receptors: Nicotinic
nAChRs are ligand-gated ion channels having a higher affinity for nicotine than ACh or muscarine.
They are classified into NM, or muscle type and NN, or neuronal type.
NM receptors are present at the neuromuscular junction, while NN receptors are present in the autonomic ganglia and the adrenal medulla.
Structurally, nicotinic receptors are rosette-shaped pentamers having a central pore. The pore serves as the ion channel. On the extracellular domain of the receptor, two ACh binding sites are present.
NM receptors comprise alpha, beta, gamma, and delta subunits, whereas NN receptors are composed of only alpha and beta subunits.
Ligand binding to the receptor opens the ion channel to cations such as sodium ions, potassium ions, and calcium ions.
Ion influx depolarizes the end plate, causing either muscle contraction at the neuromuscular junction or nerve impulse continuation at the autonomic ganglia.
5.6:
Cholinergic Receptors: Nicotinic
Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to agonists and antagonists. The neuromuscular junction possesses the NM type, whereas the CNS, PNS, and non-neuronal tissues have the NN type. D-tubocurarine, succinylcholine, and decamethonium block the NM receptors, while trimethaphan and hexamethonium block the NN receptors.
Nicotinic receptors have pentameric subunits (α, β, γ, ε, and δ) that form a rosette-like receptor complex. NM receptors have α2, β, γ (or ε), and δ subunits, while NN receptors have only α or α, β subunits. Each subunit has an intracellular C-terminus, an extracellular N-terminus, and four α helical transmembrane domains around a central pore that serves as the ion channel. On the extracellular domain of the receptors, two acetylcholine binding sites exist at the αγ and αδ interfaces.
Acetylcholine binding to nicotinic receptors causes a change in cell membrane permeability, allowing cation movement through the ion channel. Cation flux depolarizes the end plate, resulting in the contraction of muscles at the neuromuscular junction or nerve impulse continuation at the autonomic ganglia.