Ionotropic neurotransmitters, receptor

A variety of substances have been found to serve as neurotransmitters in the nervous system. Most of these have actions outside the nervous system as well. Classically, the term neurotransmitter implies ionotropic actions on neurons, while those with metabotropic actions are regarded as neuromodulators. This distinction is blurred, however, by the fact that many substances can have either action, depending on the receptor to which it binds. Table 2.1 summarizes the major classes of neurotransmitters and their receptor-effector mechanisms. 

There are two major types of receptor which are activated by neurotransmitters. These are the ionotropic and metabotropic receptors. The former receptor type is illustrated by the amino acid neurotransmitter receptors for glutamate, gamma-aminobutyric acid (GABA) and glycine, and the acetylcholine receptors of the nicotinic type. These are examples of fast transmitters in that they rapidly open and close the ionic channels in... 

In contrast to the ionotropic receptors, the metabotropic receptors are monomeric in structure and unique in that they show no structural similarity to the other G-protein-coupled neurotransmitter receptors. They are located both pre- and postsynaptically and there is experimental evidence that they are involved in synpatic modulation and excitotoxicity, functions which are also shared with the NMDA receptors. To date, no drugs have been developed for therapeutic use which are based on the modulation of these receptors. 

Since many toxins act on ion channels, they provide a wealth of chemical tools for studying the function of these channels. In fact, much of our current understanding of the properties of ion channels comes from studies utilizing only a small percentage of the highly potent and selective toxins that are now available. The toxins typically target voltage-sensitive ion channels, but a number of very useful toxins block ionotropic neurotransmitter receptors. Table 21-1 lists some of the toxins most commonly used in research, their mode of action, and their source. 

Information transfer between two neurons or between neurons and effector cells involves the release of chemical substances, which then act on the target cell by binding to appropriate receptors embedded in the plasma membrane. This process, as originally described by Otto Loewi (Loewi 1921), is termed chemical neurotransmission and occurs at contact sites known as synapses. Neurotransmitters exert their effects via members of two major families of receptors ionotropic and metabotropic neurotransmitter receptors. Activation of ionotropic receptors leads to an increase in the ion conductance of the membrane within a time scale of milliseconds or even less, whereas activation of metabotropic receptors results in slow effects (within seconds or even minutes) which involve more or less complex signaling cascades. Accordingly, information transfer via ionotropic receptors is called fast synaptic transmission, whereas the slow counterpart is called neuromodulation (Kaczmarek and Levitan 1987). 

As I described in another chapter, epidermal keratinocytes carry a series of receptors, which were originally found in the central nervous system as neurotransmitter receptors. These receptors can be categorized in two groups, that is, ionotropic receptors and G-protein-coupled receptors. 

Ionotropic neurotransmitter receptors — neurotransmitter-gated ion channels... 

Many of the methods described in the previous section have been applied to the study of multiprotein complexes in the nervous system. The first proteomic study of a neurotransmitter receptor complex in 2000 (Husi et al. 2000) has been followed by similar studies of important classes of brain receptors and channels (Table 1). As shown in Table 1, complexes associated with ion channels such as members of the ionotropic class of glutamate receptors and GPCRs such as the metabotropic class of glutamate receptors have been described. Here we review a number of such complexes and discuss how their components relate to nervous system biology. 

As with most other neurotransmitter receptors, acetylcholine receptors are classified into ionotropic and metabotropic receptors. Ionotropic acetylcholine receptors are referred to as "nicotinic" because they are responsive to nicotine, an alkaloid compound present in cigarettes. Metabotropic acetylcholine receptors are referred to as "muscarinic" because they are sensitive to muscarine, a mushroom compound. Cholesterol has been reported to modulate the activity of both receptor types, yet most studies have been focused on the interaction... 

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