Muscle-type nicotinic acetylcholine receptor structure, function, and pharmacology.

Abstract

Nicotinic acetylcholine receptors mediate fast chemical transmission throughout the central and peripheral nervous systems. The nicotinic receptor subtype found on the motor endplate at the neuromuscular junction has been an important model system for understanding receptor structure, function, signaling, and pharmacology. The nicotinic receptor found in the electric organs of fish, including the Torpedo ray, is homologous to the human muscle-type nicotinic receptor and serves as an abundant natural source for biochemical and structural studies. Here we leverage the Torpedo nicotinic receptor in structural biology and electrophysiological studies to understand how clinically relevant drug classes regulate receptor conformation and activity. The findings reveal how different types of functional antagonists stabilize distinct non-conducting states to inhibit neuromuscular transmission.