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  Peptide-toxin tools for probing the expression and function of fetal and adult subtypes of the nicotinic acetylcholine receptor

Teichert, R. W., Garcia, C. C., Potian, J. G., Schmidt, J. J., Witzemann, V., Olivera, B. M., et al. (2008). Peptide-toxin tools for probing the expression and function of fetal and adult subtypes of the nicotinic acetylcholine receptor. Annals of the New York Academy of Sciences, 1132, 61-70. doi:10.1196/annals.1405.015.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-0A37-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-DE53-9
Genre: Journal Article

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AnnNYAS_1132_2008_61.pdf (Any fulltext), 312KB
 
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 Creators:
Teichert, Russel W., Author
Garcia, Carmen C., Author
Potian, Joseph G., Author
Schmidt, James J., Author
Witzemann, Veit1, 2, Author              
Olivera, Baldomero M., Author
McArdle, Joseph J., Author
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              

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Free keywords: acetylcholine receptor; nAChR; fetal nAChR; adult nAChR; conotoxin; αA-conotoxin; Waglerin
 Abstract: 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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Language(s): eng - English
 Dates: 2008-06-282008-06-28
 Publication Status: Published in print
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
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Title: Annals of the New York Academy of Sciences
  Other : Ann. N.Y. Acad. Sci.
Source Genre: Journal
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Publ. Info: New York : New York Academy of Sciences
Pages: - Volume / Issue: 1132 Sequence Number: - Start / End Page: 61 - 70 Identifier: ISSN: 0077-8923
CoNE: https://pure.mpg.de/cone/journals/resource/954926958894_2