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Signal transmission in ligand‐gated receptors
Author(s) -
Gage Peter W
Publication year - 1998
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1046/j.1440-1711.1998.00763.x
Subject(s) - ion channel , ligand gated ion channel , biophysics , light gated ion channel , chemistry , cys loop receptors , neurotransmission , receptor , gabaa receptor , patch clamp , ion channel linked receptors , voltage gated ion channel , gating , membrane potential , chloride channel , nicotinic agonist , biochemistry , biology , nicotinic acetylcholine receptor , agonist , metabotropic glutamate receptor
At synapses, a transmitter released from a pre‐synaptic terminal binds to specific, ligand‐gated receptors in the post‐synaptic membrane to open up ion channels through the receptor molecules. The flow of ions through these channels generates electrical signals. Electrophysiological techniques have been used over the past 50 years to understand transmission of these signals at synapses. The most recent of these, the patch‐clamp technique, allows very small picoamp currents through single‐channel molecules to be recorded but gives little information about receptor structure or how drugs influence their function. Now, the subunits of most ligand‐gated ion channels have been cloned and sequenced. Cryo‐electronmicroscopy has revealed the structure of the ion channel activated by nicotinic agonists. It is pentameric and only a small part of it is in the membrane. In spite of this simple structure, the conductance of chloride channels activated by gamma‐aminobutyric acid (GABA A channels) is very variable and can be increased markedly by drugs such as diazepam. Site‐directed mutagenesis and labelling of cysteine residues in the open and the closed states are being used to define the residues that line the ion channel. Similar methods are being used to find the way in which drugs such as general anaesthetics modulate the function of GABA A receptors.