Structural mechanisms of activation and desensitization in neurotransmitter-gated ion channels.
Ion channels gated by neurotransmitters are present across metazoans, in which they are essential for brain function, sensation and locomotion; closely related homologs are also found in bacteria. Structures of eukaryotic pentameric cysteine-loop (Cys-loop) receptors and tetrameric ionotropic glutamate receptors in multiple functional states have recently become available. Here, I describe how these studies relate to established ideas regarding receptor activation and how they have enabled decades' worth of functional work to be pieced together, thus allowing previously puzzling aspects of receptor activity to be understood.
Leibniz-Institut für Molekulare Pharmakologie (FMP), Berlin, Germany.|NeuroCure, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Andrew J R
0000-0001-6062-0832
AJ
Plested
D000818:Animals; D001419:Bacteria / Q000737:chemistry / Q000378:metabolism; D001581:Benzothiadiazines / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D058466:Cysteine Loop Ligand-Gated Ion Channel Receptors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007559:Ivermectin / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008958:Models, Molecular; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010465:Perception / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D001581:Benzothiadiazines; D058466:Cysteine Loop Ligand-Gated Ion Channel Receptors; D007473:Ion Channels; D018377:Neurotransmitter Agents; D010880:Piperidines; D017470:Receptors, Glutamate; D007559:Ivermectin; C004639:cyclothiazide; C010739:ifenprodil