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Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001.

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Neuroscience. 2nd edition.

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Glutamate Receptors

Several types of ionotropic glutamate receptors have been identified. Three of these are ligand-gated ion channels called NMDA receptors, AMPA receptors, and kainate receptors (Figure 7.11C). These glutamate receptors are named after the agonists that activate them: NMDA (N-methyl-D-aspartate), AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate), and kainic acid. All of the ionotropic glutamate receptors are nonselective cation channels, allowing the passage of Na+ and K+, and in some cases small amounts of Ca2+. Like nACh receptors, the postsynaptic currents produced have a reversal potential close to 0 mV; hence AMPA, kainate, and NMDA receptor activation always produces excitatory postsynaptic responses. And, like other ligand-gated channel receptors, AMPA/kainate and NMDA receptors are formed from the association of several protein subunits that can combine in many ways to produce a large number of receptor isoforms (see Figure 7.11C).

The NMDA subfamily of glutamate receptors also form multisubunit, nonselective cation channels similar to most other ligand-gated ion channel receptors (Figure 7.12A). These receptors, however, have especially interesting properties. Perhaps most significant is the fact that NMDA receptor ion channels allow the entry of Ca2+ in addition to monovalent cations such as Na+ and K+. As a result, EPSPs produced by NMDA receptors can increase the concentration of Ca2+ within the postsynaptic neuron; the Ca2+ concentration change can then act as a second messenger to activate intracellular signaling cascades (see Chapter 8). Other unique properties of NMDA receptors are that opening the channel requires the presence of a co-agonist (the amino acid glycine), and that extracellular Mg2+ blocks the channel at hyperpolarized, but not depolarized, voltages (Figure 7.12B). Hence, NMDA receptors allow the passage of cations only when the Mg2+ block is removed by the depolarization of the postsynaptic cell, either by a large number of excitatory inputs or by the repetitive firing of the presynaptic cell. These properties are widely thought to be the basis for some forms of information storage at synapses, as described in Chapter 25. There are at least five forms of NMDA receptor subunits (NMDA-R1, and NMDA-R2A through NMDA-R2D); different synapses have distinct combinations of these subunits, producing a variety of NMDA receptor-mediated postsynaptic responses.

Figure 7.12. NMDA and AMPA/kainate receptors.

Figure 7.12

NMDA and AMPA/kainate receptors. (A) NMDA receptors contain binding sites for glutamate and the co-activator glycine, as well as an Mg2+-binding site in the pore of the channel. At hyperpolarized potentials, the electrical driving force on Mg2+ drives (more...)

While some glutamatergic synapses have only AMPA or only NMDA receptors, most have both AMPA and NMDA receptors. An antagonist of NMDA receptors, APV (2-amino-5-phosphono-valerate), is often used to differentiate between the two receptor types. The use of this drug has also revealed differences between the EPSPs produced by NMDA and those produced by AMPA/kainate receptors, such as the fact that the synaptic currents produced by NMDA receptors are slower and longer-lasting than the those produced by AMPA/kainate receptors (see Figure 7.12C).

In addition to these ionotropic glutamate receptors, there are three types of metabotropic glutamate receptor (mGluRs) (Figure 7.13). These receptors, which modulate postsynaptic ion channels indirectly, differ in their coupling to intracellular messengers (see Chapter 8) and in their sensitivity to pharmacological agents. Activation of many of these receptors leads to inhibition of postsynaptic Ca2+ and Na+ channels. Unlike the excitatory ionotropic glutamate receptors, mGluRs cause slower postsynaptic responses that can either increase or decrease the excitability of postsynaptic cells. Hence the physiological roles of mGluRs are quite varied.

Figure 7.13. Structure and function of metabotropic receptors.

Figure 7.13

Structure and function of metabotropic receptors. (A) The transmembrane architecture of metabotropic receptors. These monomeric proteins contain seven transmembrane domains. Portions of domains II, III, VI, and VII make up the neurotransmitter-binding (more...)

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By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2001, Sinauer Associates, Inc.
Bookshelf ID: NBK10802


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