New hypotheses and predictions have arisen from recent work revealing atomic-scale or near-atomic-scale structures of receptors in the 'Cys-loop' superfamily. How general is the cation-pi interaction between the natural ligand and a tryptophan residue in the aromatic box, and does this interaction extend to other ligands? What is the pathway from the binding site to gating, and what are the conformational changes during gating and desensitization? Is current flow through intracellular 'portals' in the wall of the channel a general feature? This article discusses these and related questions, emphasizing nicotinic ACh receptors and also discussing data from other members of this superfamily.
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http://dx.doi.org/10.1016/j.tins.2004.04.002 | DOI Listing |
Q Rev Biophys
January 2025
Faculty of Medicine, Department of Biophysics and Neuroscience, Wroclaw Medical University, Wrocław, Poland.
The GABA type A receptor (GABAR) belongs to the family of pentameric ligand-gated ion channels and plays a key role in inhibition in adult mammalian brains. Dysfunction of this macromolecule may lead to epilepsy, anxiety disorders, autism, depression, and schizophrenia. GABAR is also a target for multiple physiologically and clinically relevant modulators, such as benzodiazepines (BDZs), general anesthetics, and neurosteroids.
View Article and Find Full Text PDFToxicol Lett
January 2025
Bundeswehr Institute for Pharmacology and Toxicology, Neuherbergstraße 11, 80937 Munich, Germany. Electronic address:
The nicotinic acetylcholine receptor (nAChR) is a pentameric ligand-gated ion channel (pLGIC) commonly used as a model for receptors belonging to the Cys-loop superfamily. Members of pLGICs are standardly used in numerous toxicological investigations e.g.
View Article and Find Full Text PDFMed Sci Monit
January 2025
Department of Otorhinolaryngology Head and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
BACKGROUND The precedence effect (PE) is a physiological phenomenon for accurate sound localization in a reverberant environment. Physiological studies of PE have mostly focused on the central nucleus of the inferior colliculus (CNIC), which receives ascending and descending projections, as well as projections from the shell of the inferior colliculus (IC) and contralateral IC. However, the role of the dorsal cortex of the IC (DCIC), which receives ascending and descending projections to ensure sound information processing and conduction on PE formation, remains unclear.
View Article and Find Full Text PDFSheng Li Xue Bao
December 2024
Department of Clinical Psychology, Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250117, China.
Glycine receptors (GlyRs) belong to the ligand-gated ion channel receptor superfamily and are widely distributed throughout the central nervous system. GlyRs are essential for maintaining visual, auditory, sensory and motor functions, and abnormalities in its structure and function can lead to various neurological disorders. This review aims to provide an extensive analysis of the structure, function and regulatory mechanisms of GlyRs, and evaluate its role in various central nervous system diseases.
View Article and Find Full Text PDFNat Commun
January 2025
State Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, 300350, China.
The zinc-activated channel (ZAC) is an atypical mammalian cys-loop receptor (CLR) that is activated by zinc ions and protons, allowing cations to pass through. The molecular mechanism that ligands use to activate ZAC remains elusive. Here, we present three cryo-electron microscopy reconstructions of human ZAC (hZAC) under different conditions.
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