Neurotransmitter receptors can be categorized into two major groups: ligand-gated ion channels, also known as ionotropic receptors, and G protein-coupled receptors, also referred to as metabotropic receptors (Fig. 6.12A–B). Most classic neurotransmitters and neuropeptides possess at least one metabotropic receptor. Additionally, many classic neurotransmitters have at least one ionotropic receptor. Ionotropic receptors are protein complexes that feature both an extracellular binding site for the transmitter and an ion channel, or pore, across the cell membrane. Typically composed of three to five protein subunits, each with several membrane-spanning domains, ionotropic receptors undergo changes in the probability of the ion channel being in an open state upon neurotransmitter binding, resulting in rapid postsynaptic events with a duration of several milliseconds. These receptors play a vital role in the generation of fast synaptic EPSPs and IPSPs, as previously discussed.
Ionotropic receptors can be divided into several superfamilies. Members of the cys-loop superfamily consist of peptide subunits with an N-terminal extracellular domain that contains a loop delimited by cysteine residues. This superfamily includes ionotropic receptors for acetylcholine, serotonin, GABA, and glycine. Alongside their defining cysteine loop, these receptors share common characteristics: they are pentamers, with each peptide subunit possessing four transmembrane domains; the neurotransmitter binds to the N-terminal domain; and the second transmembrane domains are believed to form the wall of the ion pore.
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.