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The Ion-Conducting Pore of Glutamate Receptor Channels

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Ionotropic Glutamate Receptors in the CNS

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 141))

Abstract

Ionotropic glutamate receptors (GluRs) mediate the postsynaptic response at most excitatory synapses in the brain. A variety of G1uR channel subtypes provides these synapses with a repertoire of distinct computational properties, many of which arise from ionic interactions with the channel pore. In both N-methyl-D-aspartate receptor (NMDAR) and a-amino-3-hydroxy-5methylisoxazole-4-propionic acid receptor (AMPAR) channels, a voltage-dependent blocking process renders the response of the channel dependent on the concurrent activity of the synapse. The voltage dependence of extra-cellular Mg2+ block in NMDAR (Mayer et al. 1984; Nowak et al. 1984) and cytoplasmic polyamine block in AMPAR channels (Bowie and Mayer 1995; Donevan and Rogawskj 1995; Isa et al. 1995; Kamboj et al. 1995; Koh et al.1995) allows these transmembrane proteins to integrate pre-and postsynaptic signals. Furthermore, Ca2+ influx through G1uR channels can trigger long-lasting changes in synaptic strength (Bliss and Collingridge 1993) but can also lead to cell death under pathological conditions (Choi 1988; Meldrum and Garthwaite 1990). The amount of Ca2+ entering a neuron during receptor activation may determine the nature and persistence of the postsynaptic response (Berridge 1998). Thus, the control of Ca2+ influx by voltage-dependent blocking mechanisms is essential for the role of GluRs in synaptic plasticity as a basis of higher brain functions, such as learning and memory. Given the physiological and pathophysiological relevance of ionic mechanisms in G1uR function, understanding the structural basis of ion permeation and blocking in these receptor channels is of the utmost interest.

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Abbreviations

3D:

Three dimensional

3TM:

Three transmembrane

5-HT3R:

5-hydroxytryptamine (serotonin) type-3 receptor

AChR:

Acetylcholine receptor

AMPA:

α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid

AMPAR:

AMPA receptor

BU:

Bead units

Ca channel:

Voltage-gated calcium channel

CNG:

Cyclic-nucleotide-gated

EDTA:

Ethylene diamine tetraacetic acid

GABAAR:

γ-Aminobutyric acid type A receptor

G1uR:

Glutamate receptor

G1yR:

Glycine receptor

nAChR:

Nicotinic acetylcholine receptor

MTSES:

2-Sulfonatoethyl-methanethiosufonate

MTSET:

2-Trimethylammonioethyl-methanethiosufonate

NMDAR:

N-methyl-D-aspartate receptor

SCAM:

Substituted-cysteine-accessibility method

SEM:

Standard error of the mean

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Authors
  1. T. Kuner
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  2. L. P. Wollmuth
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  3. B. Sakmann
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Editors and Affiliations

  1. Physiologisches Institut, Albert-Ludwigs-Universität Freiburg, Hermann-Herder-Str. 7, D-79104, Freiburg, Germany

    Peter Jonas

  2. ZMBH, Im Neuenheimer Feld 282, D-69120, Heidelberg, Germany

    Hannah Monyer

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Kuner, T., Wollmuth, L.P., Sakmann, B. (1999). The Ion-Conducting Pore of Glutamate Receptor Channels. In: Jonas, P., Monyer, H. (eds) Ionotropic Glutamate Receptors in the CNS. Handbook of Experimental Pharmacology, vol 141. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-08022-1_6

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  • DOI: https://doi.org/10.1007/978-3-662-08022-1_6

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