The electrical signals between nerve cells and their targets are transmitted at high speed through the action of transmitter-gated ion channels. These fast-acting molecular switches are multimeric proteins composed of two main functional units: an extracellular ligand-binding domain, and a gated membrane-spanning pore. When the neurotransmitter, released from the nerve terminus, enters the ligand-binding domain on the surface of the target cell, the ligand-binding domain changes its conformation transiently. As a result of this change the gate in the membrane-spanning pore opens and ions pass through the gate selectively. An atomic model of the closed pore of the nicotinic acetylcholine receptor, one of several transmitter-gated ion channels, was obtained by electron microscopy, and the mechanism of signal transmission was revealed. The nicotinic acetylcholine receptor controls electrical signaling between nerve and muscle cells by opening and closing a gate of the membrane-spanning pore.
The pore consists of five subunits, each containing four alpha-helices. It is composed of an inner ring of 5 alpha-helices and an outer ring of 15 alpha-helices derived from all five subunits. The inner ring forms the radial ion pathway. The outer ring coils around each other and thus shields the inner ring from the lipid. The gate is located at the center of the lipid bilayer and formed by weak interactions between neighboring inner helices. When acetylcholine enters the ligand-binding domain, which consists of some beta-sheets in the alpha-subunits above the entrance of the pore, rotation of adjacent protein chains is triggered. These rotations are communicated through the inner helices, and destabilize and open the gate of the pore by breaking the hydrophobic barrier. In consequence, the cations such as potassium, calcium, and sodium ions pass through the pore selectively. According to this mechanism, the electrical signals released from the nerve cells are transmitted.
Protein Data Bank (PDB)
Miyazawa, A. Fujiyoshi, Y. Unwin, N.; "Structure and Gating Mechanism of the Acetylcholine Receptor Pore"; Nature; (2003) 423:949-955. PubMed:12827192
author: Yuko Tsuchiya