Neurotransmitter receptors are members of one of two large groups or families of proteins: ligand-gated ion channels, also known as ionotropic receptors, and G protein– coupled receptors, also referred to as metabotropic receptors (
Fig. 6.12A–B ). Almost all classic neurotransmitters and neuropeptides have at least one metabotropic-type receptor. Many of the classic neurotransmitters also have at least one ionotropic receptor. Ionotropic receptors are protein complexes that both have an extracellular binding site for the transmitter and form an ion channel (pore) through the cell membrane. The receptor is made up of several protein subunits, usually three to five, each of which typically has a series of membrane-spanning domains, some of which contribute to the wall of the ion channel. Binding of the neurotransmitter alters (usually increases) the probability of the ion channel being in the open state and thus typically results in postsynaptic events that are rapid in both onset and decay, with a duration of several milliseconds. Ionotropic receptors underlie fast synaptic EPSPs and IPSPs, as described earlier.
Theionotropicreceptorscanbedividedintoseveralsuperfamilies.Membersofthecys-loopsuperfamilyhavepeptidesubunitsthathaveanN-terminalextracellulardomainthatcontainsaloopdelimitedbycysteineresidues.Thisfamilyincludestheionotropicreceptorsforacetylcholine,serotonin,GABA,andglycine.Inadditiontotheirfamily-definingcysteineloop,thesereceptorssharethefollowingcommonfeatures:theyarepentamers,witheachpeptidesubunithavingfourtransmembranedomains;theneurotransmitterbindstotheN-terminaldomain;andthesecondtransmembranedomainsarethoughttoformthewalloftheionpore.