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11: Modulation of Synaptic Transmission: Second Messengers

Introduction

  • The Cyclic AMP Pathway Is the Best Understood Second Messenger Signaling Cascade Initiated by G Protein-Coupled Receptors

  • The Second-Messenger Pathways Initiated by G Protein-Coupled Receptors Share a Common Molecular Logic

    • A Family of G Proteins Activates Distinct Second-Messenger Pathways

    • Hydrolysis of Phospholipids by Phospholipase C Produces Two Important Second Messengers, IP3 and Diacylglycerol

    • Hydrolysis of Phospholipids by Phospholipase A2 Liberates Arachidonic Acid to Produce Other Second Messengers

  • Transcellular Messengers Are Important for Regulating Presynaptic Function

    • Endocannabinoids Are Derived from Arachidonic Acid

    • The Gaseous Second Messengers, Nitric Oxide and Carbon Monoxide, Stimulate Cyclic GMP Synthesis

  • A Family of Receptor Tyrosine Kinases Mediates Some Metabotropic Receptor Effects

  • The Physiological Actions of Ionotropic and Metabotropic Receptors Differ

    • Second-Messenger Cascades Can Increase or Decrease the Opening of Many Types of Ion Channels

    • G Proteins Can Modulate Ion Channels Directly

    • Cyclic AMP-Dependent Protein Phosphorylation Can Close Potassium Channels

  • Synaptic Actions Mediated by Phosphorylation Are Terminated by Phosphoprotein Phosphatases

  • Second Messengers Can Endow Synaptic Transmission with Long-Lasting Consequences

  • An Overall View

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 Chapter 8, the type of action depends on the type of receptor. Activation of ionotropic receptors directly opens ion channels that are part of the receptor macro molecule itself. In contrast, activation of metabotropic receptors regulates the opening of ion channels indirectly through biochemical signaling pathways. The receptor and ion channels that are affected are distinct macromolecules (Figure 11–1).

Figure 11–1
Neurotransmitter actions can be divided into two groups according to the way in which receptor and effector functions are coupled.

A. Direct transmitter actions are produced by ionotropic receptors, ligand-gated channels in which the receptor and ion channel are domains formed by a single macromolecule. The binding of transmitter to the receptor on the extracellular aspect of the protein directly opens the ion channel embedded in the cell membrane.

B. Indirect transmitter actions are caused by binding of transmitter to metabotropic receptors that are separate macromolecules from the ion channels that 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 of the kinase itself on tyrosine residues.

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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 mediate behaviors, from simple reflexes to complex cognitive processes. Metabotropic receptors modulate behaviors; they modify reflex strength, help focus attention, set ...

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