Ligand-gated channel: postsynaptic receptors and drug targets

Rapid synaptic transmission depends on the activation of ligand-gated channels by neurotransmitters. The molecular characterization of these membrane proteins has provided a valuable framework for investigating basic synaptic mechanisms and for developing pharmacologic strategies for the manipulation of neural function. This chapter begins with a summary of present molecular knowledge about different classes of ligand-gated channels, including the acetylcholine-gamma-aminobutyric acid (GABA) receptor superfamily, the excitatory amino acid receptor superfamily, and purine receptors. The activation mechanisms of ligand-gated channels are discussed in terms of detailed allosteric models that involve conformational transitions coupled with the occupation of binding sites by ligands. In addition to providing a quantitative understanding of the postsynaptic aspects of synaptic transmission, these allosteric models have been used to clarify the action of drugs that serve as valuable tools for the investigation and management of epilepsy. Relating these physical theories of receptor function to molecular structure represents a growing field of research on the nervous system.