Identification of a site in glutamate receptor subunits that controls calcium permeability.
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.
Hume
R I
RI
Molecular Neurobiology Laboratory, Salk Institute, La Jolla, CA 92037.
Dingledine
R
R
Heinemann
S F
SF
D000595:Amino Acid Sequence; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003001:Cloning, Molecular; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology; D014981:Xenopus
D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001464:Barium; D012964:Sodium; D002118:Calcium