Presence of multiple binding sites on α9α10 nAChR receptors alludes to stoichiometric-dependent action of the α-conotoxin, Vc1.1.
Dinesh C. Indurthi,Elena Pera,Hye Lim Kim,Cindy Chu,Malcolm D. McLeod,J. Michael McIntosh,J. Michael McIntosh,Nathan L. Absalom,Mary Chebib +8 more
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TLDR
Using 2-electrode voltage clamp methods and maintaining a constant intracellular Ca(2+) concentration, this study observed a biphasic activation curve for ACh that is dependent on receptor stoichiometry and infer that there is an additional binding site for A Ch and Vc1.1 at the α9-α9 interface on the hypothesized (α9)₃(α10)⁂ nAChR.About:
This article is published in Biochemical Pharmacology.The article was published on 2014-05-01 and is currently open access. It has received 30 citations till now. The article focuses on the topics: Nicotinic agonist & Acetylcholine receptor.read more
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Journal ArticleDOI
Conotoxins Targeting Nicotinic Acetylcholine Receptors: An Overview
TL;DR: An overview of the knowledge the authors have today on the molecular pharmacology of conotoxins specifically interacting with nAChRs along with the structure–function relationship data is given.
Journal ArticleDOI
Crystal structures of free and antagonist-bound states of human α9 nicotinic receptor extracellular domain
Marios Zouridakis,Petros Giastas,Eleftherios Zarkadas,Dafni Chroni-Tzartou,Piotr Bregestovski,Socrates J. Tzartos,Socrates J. Tzartos +6 more
TL;DR: The X-ray crystal structures of the α9 ECD revealed a functionally important β7-β10 strand interaction in α9-containing nAChRs, involving their unique Thr147, a hydration pocket similar to that of mouse α1 ECD and a membrane-facing network coordinated by the invariant Arg210.
Journal ArticleDOI
Crystal Structure of the Monomeric Extracellular Domain of α9 Nicotinic Receptor Subunit in Complex With α-Conotoxin RgIA: Molecular Dynamics Insights Into RgIA Binding to α9α10 Nicotinic Receptors.
Marios Zouridakis,Athanasios Papakyriakou,Igor Ivanov,Igor E. Kasheverov,Igor E. Kasheverov,Victor I. Tsetlin,Victor I. Tsetlin,Socrates J. Tzartos,Socrates J. Tzartos,Petros Giastas +9 more
TL;DR: The 2.26-A resolution crystal structure of α9-ECD in complex with α-conotoxin (α-Ctx) RgIA, a potential drug for chronic pain, was reported in this paper.
Journal ArticleDOI
αS-conotoxin GVIIIB potently and selectively blocks α9α10 nicotinic acetylcholine receptors.
Sean Christensen,Pradip K. Bandyopadhyay,Baldomero M. Olivera,J. Michael McIntosh,J. Michael McIntosh +4 more
TL;DR: The S-superfamily represents a novel conotoxin scaffold for flexibly targeting a variety of receptor subtypes, including the α9α10 nAChR subtype, and Pharmacological characterization of αS-GVIIIB shows that it is over 100-fold selective for the β- face of the α10 rather than the (+) face of this subunit as critical to binding of α9 α10-targeted conotoxins.
Journal ArticleDOI
Differential Contribution of Subunit Interfaces to α9α10 Nicotinic Acetylcholine Receptor Function.
Juan Carlos Boffi,Irina Marcovich,JasKiran K. Gill-Thind,Jeremias Corradi,Toby Collins,Marcela Lipovsek,Marcelo J. Moglie,Paola V. Plazas,Patricio O. Craig,Neil S. Millar,Cecilia Bouzat,Ana Belén Elgoyhen +11 more
TL;DR: It is concluded that asymmetry in the contribution of subunit interface domains to α9α10 receptors results from adaptive amino acid changes acquired only during the evolution of mammalian α10 subunits.
References
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Journal ArticleDOI
Refined Structure of the Nicotinic Acetylcholine Receptor at 4A Resolution
TL;DR: A comparison of the structure of the alpha subunit with that of AChBP having ligand present, suggests how the localised rearrangement overcomes the distortions and initiates the rotational movements associated with opening of the channel.
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Structure and Gating Mechanism of the Acetylcholine Receptor Pore.
TL;DR: An atomic model of the closed pore of the nicotinic acetylcholine receptor, obtained by electron microscopy of crystalline postsynaptic membranes, is presented.
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α9: An acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells
TL;DR: The results suggest that the α9 receptor is involved in the cholinergic efferent innervation of cochlear hair cells and thus may modulate the encoding of auditory stimuli.
Journal ArticleDOI
α10: A determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells
Ana Belén Elgoyhen,Douglas E. Vetter,Eleonora Katz,Carla V. Rothlin,Stephen F. Heinemann,Jim Boulter +5 more
TL;DR: The cloning and characterization of rat α10 are reported, a previously unidentified member of the nicotinic acetylcholine receptor (nAChR) subunit gene family, and data suggest that efferent modulation of hair cell function occurs, at least in part, through heteromeric nAChRs assembled from both α9 and α10 subunits.
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A transient calcium‐dependent chloride current in the immature Xenopus oocyte.
TL;DR: Ionic currents were studied in immature full‐grown Xenopus oocytes using the two‐micro‐electrode voltage‐clamp technique and the outward peak in records of total membrane current represented the contribution of a transient outward current carried by Cl ions which was dependent on the entry of external Ca.