THE BINDING OF NEUROTRANSMITTER to postsynaptic receptors produces a postsynaptic potential either directly, by opening ion channels, or indirectly, by altering ion channel activity through changes in the postsynaptic cell’s biochemical state. As we saw in Chapters 11 to 13, the type of postsynaptic action depends on the type of receptor. Activation of an ionotropic receptor directly opens an ion channel that is part of the receptor macromolecule itself. In contrast, activation of metabotropic receptors regulates the opening of ion channels indirectly through biochemical signaling pathways; the metabotropic receptor and the ion channels regulated by the receptor are distinct macromolecules (Figure 14–1).
Neurotransmitter actions can be divided into two groups according to the way receptor and effector functions are coupled.
A. Direct transmitter actions are produced by the binding of transmitter to ionotropic receptors, ligand-gated channels in which the receptor and ion channel are domains within a single macromolecule. The binding of transmitter to the receptor on the extracellular aspect of the receptor-channel protein directly opens the ion channel embedded in the cell membrane.
B. Indirect transmitter actions are caused by binding of transmitter to metabotropic receptors, macromolecules that are separate from the ion channels they regulate. There are two families of these receptors. 1. G protein–coupled receptors activate guanosine triphosphate (GTP)-binding proteins that engage a second-messenger cascade or act directly on ion channels. 2. Receptor tyrosine kinases initiate a cascade of protein phosphorylation reactions, beginning with autophosphorylation (P) of the kinase itself on tyrosine residues.
Whereas the action of ionotropic receptors is fast and brief, metabotropic receptors produce effects that begin slowly and persist for long periods, ranging from hundreds of milliseconds to many minutes. The two types of receptors also differ in their functions. Ionotropic receptors underlie fast synaptic signaling that is the basis of all behaviors, from simple reflexes to complex cognitive processes. Metabotropic receptors modulate behaviors; they modify reflex strength, activate motor patterns, focus attention, set emotional states, and contribute to long-lasting changes in neural circuits that underlie learning and memory. Metabotropic receptors are responsible for many of the actions of transmitters, hormones, and growth factors. The actions of these neuromodulators can produce remarkable and dramatic changes in neuronal excitability and synaptic strength and, in so doing, can profoundly alter the state of activity in an entire circuit important for behavior.
Ionotropic receptors change the membrane potential quickly. As we have seen, this change is local at first but is propagated as an action potential along the axon if the change in membrane potential is suprathreshold. Activation of metabotropic receptors also begins as a local action that can spread to a wider region of the cell. The binding of a neurotransmitter with a metabotropic receptor activates proteins that in turn activate effector enzymes. The effector enzymes ...