MuscletypenAChR

MuscletypenAChR, also known as the muscle-type nicotinic acetylcholine receptor, is a pentameric ligand-gated ion channel that mediates synaptic transmission at the vertebrate neuromuscular junction. It belongs to the Cys-loop receptor superfamily and is located in the postsynaptic membrane of the skeletal muscle endplate.

In adult skeletal muscle, the receptor is composed of two α1 subunits and one each of β1, δ, and ε subunits (α12β1δε). During fetal development, the ε subunit is replaced by γ (α12β1δ1γ1). The receptor is densely clustered at the motor endplate by the cytoplasmic protein rapsyn and is anchored to the cytoskeleton, ensuring efficient signal transmission.

Structure and binding: Each subunit contributes an extracellular N-terminus and four transmembrane segments (M1–M4). The M2 segments line the central pore. The extracellular domain contains two acetylcholine binding sites at the interfaces between the α1 subunit and neighboring subunits (α1–δ and α1–ε/γ). Binding of two acetylcholine molecules typically activates the receptor.

Function: Upon acetylcholine release from the motor neuron, binding to the receptor induces conformational changes that open the ion channel, allowing Na+ influx and some Ca2+ influx, with concurrent K+ efflux. This generates an endplate potential that triggers muscle fiber depolarization and contraction. The receptor can desensitize with prolonged agonist exposure, reducing responsiveness.

Clinical relevance: Autoimmune antibodies against muscle-type nAChR are a major cause of myasthenia gravis, leading to reduced receptor numbers and impaired transmission. Therapies include acetylcholinesterase inhibitors to boost ACh levels and immunomodulatory approaches. Toxins such as alpha-bungarotoxin bind the receptor, while non-depolarizing antagonists like curare block it competitively. The muscle-type nAChR remains a key model for studying receptor structure and signaling at the neuromuscular junction.