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          Institute: MPI für medizinische Forschung     Collection: Arbeitsgruppe Witzemann / Koenen     Display Documents

ID: 420263.0, MPI für medizinische Forschung / Arbeitsgruppe Witzemann / Koenen
Peptide−Toxin Tools for Probing the Expression
and Function of Fetal and Adult Subtypes of the
Nicotinic Acetylcholine Receptor
Translation of Title:Peptide−Toxin Tools for Probing the Expression
and Function of Fetal and Adult Subtypes of the
Nicotinic Acetylcholine Receptor
Authors:Teichert, Russel W.; Garcia, Carmen C.; Potian, Joseph G.; Schmidt, James J.; Witzemann, Veit; Olivera, Baldomero M.; McArdle, Joseph J.
Date of Publication (YYYY-MM-DD):2008-06-01
Title of Journal:Ann. N.Y. Acad. Sci.
Journal Abbrev.:Ann. N.Y. Acad. Sci.
Start Page:61
End Page:70
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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 αAS−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 αAS−conotoxin analog,
αA−OIVA[K15N], are high−affinity, highly selective inhibitors of the adult and fetalmuscle 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, αA−OIVA[K15N] andWaglerin−1 should have further utility in determining the
roles of fetal and adult nAChR subtypes in development, in mature tissues, and under pathological
Free Keywords:acetylcholine receptor; nAChR; fetal nAChR; adult nAChR; conotoxin; αA−conotoxin;
Last Change of the Resource (YYYY-MM-DD):--
External Publication Status:published
Document Type:Article
Communicated by:wkaiser
Affiliations:MPI f�r medizinische Forschung/Arbeitsgruppe Witzemann / Koenen
External Affiliations:Department of Biology, University of Utah, Salt Lake City, Utah, USA; Department of Pharmacology and Physiology, UMDNJ−New Jersey Medical School,
Newark, New Jersey, USA; Integrated Toxicology Division, U.S. Army Medical Research Institute of Infectious
Diseases, Fort Detrick, Frederick, Maryland, USA
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