| Peptide-toxin tools for probing the expression and function of fetal and adult subtypes of the nicotinic acetylcholine receptor. | |
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MedLine Citation:
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PMID: 18567854 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although the neuromuscular nicotinic acetylcholine receptor (nAChR) is one of the most intensively studied ion channels in the nervous system, the differential roles of fetal and adult subtypes of the nAChR under normal and pathological conditions are still incompletely defined. Until recently, no pharmacological tools distinguished between fetal and adult subtypes. Waglerin toxins (from snake venom) and alphaA(S)-conotoxins (from cone-snail venom) have provided such tools. Because these peptides were characterized by different research groups using different methods, we have: 1) more extensively tested their subtype selectivity, and 2) begun to explore how these peptides may be used in concert to elucidate expression patterns and functions of fetal and adult nAChRs. In heterologous expression systems and native tissues, Waglerin-1 and an alphaA(S)-conotoxin analog, alphaA-OIVA[K15N], are high-affinity, highly selective inhibitors of the adult and fetal muscle nAChRs, respectively. We have used the peptides and their fluorescent derivatives to explore the expression and function of the fetal and adult nAChR subtypes. While fluorescent derivatives of these peptides indicated a gradual transition from fetal to adult muscle nAChRs in mice during the first 2 weeks postnatal, we unexpectedly observed a steeper transition in functional expression in the mouse diaphragm muscle using electrophysiology. As a toolkit of pharmacological agents with complementary specificity, alphaA-OIVA[K15N] and Waglerin-1 should have further utility in determining the roles of fetal and adult nAChR subtypes in development, in mature tissues, and under pathological conditions. |
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Authors:
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Russell W Teichert; Carmen C Garcia; Joseph G Potian; James J Schmidt; Veit Witzemann; Baldomero M Olivera; Joseph J McArdle |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Annals of the New York Academy of Sciences Volume: 1132 ISSN: 0077-8923 ISO Abbreviation: Ann. N. Y. Acad. Sci. Publication Date: 2008 |
Date Detail:
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Created Date: 2008-06-23 Completed Date: 2008-09-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7506858 Medline TA: Ann N Y Acad Sci Country: United States |
Other Details:
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Languages: eng Pagination: 61-70 Citation Subset: IM |
Affiliation:
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Department of Biology, University of Utah, Salt Lake City, Utah, USA. russ_teichert@yahoo.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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physiology* Animals Conotoxins / pharmacology* Crotalid Venoms / pharmacology* Electrophysiology Kinetics Oocytes / drug effects, metabolism Patch-Clamp Techniques Protein Binding Protein Subunits / classification, genetics, metabolism Receptors, Nicotinic / classification*, genetics, metabolism* Xenopus laevis |
| Chemical | |
Reg. No./Substance:
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0/Conotoxins; 0/Crotalid Venoms; 0/Protein Subunits; 0/Receptors, Nicotinic; 144856-56-4/waglerin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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