دورية أكاديمية
أعرض في EDS

αM-Conotoxin MIIIJ Blocks Nicotinic Acetylcholine Receptors at Neuromuscular Junctions of Frog and Fish.

التفاصيل البيبلوغرافية
العنوان: αM-Conotoxin MIIIJ Blocks Nicotinic Acetylcholine Receptors at Neuromuscular Junctions of Frog and Fish.
المؤلفون: Rybin MJ; Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.; Department of Psychiatry and Behavioral Sciences, University of Miami, Miller School of Medicine, Miami, FL 33136, USA., O'Brien H; Department of Biology, University of Utah, Salt Lake City, UT 84112, USA., Ramiro IBL; Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Azam L; Department of Biology, University of Utah, Salt Lake City, UT 84112, USA., McIntosh JM; Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.; George E. Whalen Veterans Affairs Medical Center, Salt Lake City, UT 84112, USA.; Department of Psychiatry, University of Utah, Salt Lake City, UT 84112, USA., Olivera BM; Department of Biology, University of Utah, Salt Lake City, UT 84112, USA., Safavi-Hemami H; Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA., Yoshikami D; Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
المصدر: Toxins [Toxins (Basel)] 2020 Mar 21; Vol. 12 (3). Date of Electronic Publication: 2020 Mar 21.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101530765 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6651 (Electronic) Linking ISSN: 20726651 NLM ISO Abbreviation: Toxins (Basel) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel : MDPI
مواضيع طبية MeSH: Conotoxins/*pharmacology , Muscle, Skeletal/*drug effects , Neuromuscular Junction/*drug effects , Nicotinic Antagonists/*pharmacology , Receptors, Nicotinic/*metabolism, Action Potentials/drug effects ; Amino Acid Sequence ; Animals ; Conotoxins/chemistry ; Dose-Response Relationship, Drug ; Excitatory Postsynaptic Potentials/drug effects ; Goldfish ; Mice ; Muscle, Skeletal/metabolism ; Neuromuscular Junction/metabolism ; Nicotinic Antagonists/chemistry ; Paresis/chemically induced ; Predatory Behavior/drug effects ; Protein Binding ; Sequence Alignment ; Species Specificity ; Xenopus laevis
مستخلص: We report the discovery and functional characterization of αM-Conotoxin MIIIJ, a peptide from the venom of the fish-hunting cone snail Conus magus . Injections of αM-MIIIJ induced paralysis in goldfish ( Carassius auratus ) but not mice. Intracellular recording from skeletal muscles of fish ( C. auratus ) and frog ( Xenopus laevis ) revealed that αM-MIIIJ inhibited postsynaptic nicotinic acetylcholine receptors (nAChRs) with an IC 50 of ~0.1 μM. With comparable potency, αM-MIIIJ reversibly blocked ACh-gated currents (I ACh ) of voltage-clamped X. laevis oocytes exogenously expressing nAChRs cloned from zebrafish ( Danio rerio ) muscle. αM-MIIIJ also protected against slowly-reversible block of I ACh by α-bungarotoxin (α-BgTX, a snake neurotoxin) and α-conotoxin EI (α-EI, from Conus ermineus another fish hunter) that competitively block nAChRs at the ACh binding site. Furthermore, assessment by fluorescence microscopy showed that αM-MIIIJ inhibited the binding of fluorescently-tagged α-BgTX at neuromuscular junctions of X. laevis, C. auratus , and D. rerio . (Note, we observed that αM-MIIIJ can block adult mouse and human muscle nAChRs exogenously expressed in X. laevis oocytes, but with IC 50 s ~100-times higher than those of zebrafish nAChRs.) Taken together, these results indicate that αM-MIIIJ inhibits muscle nAChRs and furthermore apparently does so by interfering with the binding of ACh to its receptor. Comparative alignments with homologous sequences identified in other fish hunters revealed that αM-MIIIJ defines a new class of muscle nAChR inhibitors from cone snails.
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معلومات مُعتمدة: P01 GM048677 United States GM NIGMS NIH HHS; 19063 International Velux Foundation; GM048677 United States NH NIH HHS
فهرسة مساهمة: Keywords: conotoxin; neuromuscular junction; nicotinic acetylcholine receptor; venom
المشرفين على المادة: 0 (Conotoxins)
0 (Nicotinic Antagonists)
0 (Receptors, Nicotinic)
تواريخ الأحداث: Date Created: 20200405 Date Completed: 20210305 Latest Revision: 20210305
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7150935
DOI: 10.3390/toxins12030197
PMID: 32245200
قاعدة البيانات: MEDLINE
الوصف
تدمد:2072-6651
DOI:10.3390/toxins12030197