[Molecular operation of ionotropic glutamate receptors: proteins that mediate the excitatory synaptic neurotransmission].
In the brain of vertebrates, glutamate receptor ion channels (iGluR) mediate fast neurotransmission at excitatory synapses. They exist as distinct subfamilies (AMPA, Kainate and NMDA) differing in their functional properties. Yet, all iGluR are tetramers sharing a common molecular architecture, and a common scheme applies for the general mechanisms of their activation, which are discussed in this review. The dissection of the molecular mechanisms responsible for the operation of iGluR explain how they match their physiological requirements and paves the way to new strategies for pharmacological regulations of these receptors. This could prove useful for the discovery of drugs of therapeutic interest, such as cognitive enhancers, pain killers or anti-psychotics.
Gielen
Marc
M
Laboratoire de neurobiologie, Ecole normale supérieure, CNRS, 46, rue d'Ulm, 75005 Paris, France. marc.gielen@gmail.com
D000494:Allosteric Regulation; D002412:Cations; D002491:Central Nervous System Agents / Q000494:pharmacology / Q000627:therapeutic use; D019281:Dimerization; D015195:Drug Design; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D001523:Mental Disorders / Q000188:drug therapy; D008958:Models, Molecular; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D011487:Protein Conformation; D021122:Protein Subunits; D017470:Receptors, Glutamate / Q000737:chemistry / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology; D013379:Substrate Specificity; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D002412:Cations; D002491:Central Nervous System Agents; D018690:Excitatory Amino Acid Agonists; D021122:Protein Subunits; D017470:Receptors, Glutamate; D017661:Receptors, Presynaptic; D018698:Glutamic Acid