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Science 30 August 1991:
Vol. 253. no. 5023, pp. 1028 - 1031
DOI: 10.1126/science.1653450

Articles

Science, Vol 253, Issue 5023, 1028-1031
Copyright © 1991 by American Association for the Advancement of Science


articles

Identification of a site in glutamate receptor subunits that controls calcium permeability

RI Hume, R Dingledine, and SF Heinemann

Molecular Neurobiology Laboratory, Salk Institute, La Jolla, CA 92037.

The neurotransmitter glutamate mediates excitatory synaptic transmission throughout the brain. A family of genes encoding subunits of the non-N-methyl-D-aspartate (non-NMDA) type of glutamate receptor has been cloned. Some combinations of these subunits assemble into receptors with a substantial permeability to calcium, whereas others do not. To investigate the structural features that control ion permeation through these ligand-gated channels, mutant receptor subunits with single-amino acid changes were constructed. Mutation of a certain amino acid that results in a net charge change (from glutamine to arginine or vice versa) alters both the current-voltage relation and the calcium permeability of non-NMDA receptors. A site has thus been identified that regulates the permeation properties of these glutamate receptors.


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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    PDF »
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   Abstract »    PDF »
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   Abstract »    PDF »
Control of kinetic properties of AMPA receptor channels by nuclear RNA editing.
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   Abstract »    PDF »
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   Abstract »    PDF »
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   Abstract »    PDF »
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   Abstract »    PDF »
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   Abstract »    PDF »
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B Sakmann (1992)
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   PDF »
Chloroplast RNA Editing Required for Functional Acetyl-CoA Carboxylase in Plants.
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   Abstract »    Full Text »    PDF »



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