The opening or closing of postsynaptic ion channels is accomplished in different ways by two broad families of receptor proteins, ionotropic and metabotropic receptors. Ionotropic receptors are multimers made up of at least four or five individual protein subunits, each of which contributes to the pore of the ion channel. Ionotropic receptors contain two functional domains, an extracellular site that binds neurotransmitters.
and a membrane-spanning domain that forms an ion channel. When a transmitter, or ligand, binds to an ionotropic receptor, the channel becomes activated and ions can flow through the channel. Ionotropic receptors generally mediate rapid postsynaptic effects. The postsynaptic potentials arise within a millisecond or two of an action potential invading the presynaptic terminal and last for only a few tens of milliseconds or less.
The second family of neurotransmitter receptors are the metabotropic receptors, so-called because the eventual movement of ions through a channel depends on one or more metabolic steps. Metabotropic receptors do not have ion channels as part of their structure. Instead, they affect other channels by the activation of intermediate molecules called G-proteins.
For this reason, metabotropic receptors are also called G-protein-coupled receptors. Metabotropic receptors have an extracellular domain that contains a neurotransmitter binding site and an intracellular domain that binds to G-proteins. The G-protein shown here has three subunits, alpha, beta, and gamma.
The alpha subunit binds to guanine nucleotides, either GTP or GDP. Binding of GDP allows the alpha subunit to bind to the beta and gamma subunits to form an inactive trimer. Binding of an extracellular signal activates the metabotropic receptor and causes GDP to be replaced with GTP on the alpha subunit of the G-protein. When GTP binds, the G-protein becomes activated and the alpha subunit dissociates from the beta-gamma complex.
Following activation, both the GTP-bound alpha subunit and the free beta-gamma complex can bind to downstream effector molecules that mediate a variety of responses in the target cell. For example, the G-protein may interact directly with ion channels causing the channels to open or close. Activated G-proteins may also bind to other effector proteins such as enzymes that make intracellular messengers that mediate a variety of responses in the target cell.
The activation of metabotropic receptors typically produces much slower responses, ranging from hundreds of milliseconds to minutes or even longer. A given transmitter may activate both ionotropic and metabotropic receptors to produce both fast and slow postsynaptic potentials at the same synapse.