Document Detail


Peptide-toxin tools for probing the expression and function of fetal and adult subtypes of the nicotinic acetylcholine receptor.
MedLine Citation:
PMID:  18567854     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Russell W Teichert; Carmen C Garcia; Joseph G Potian; James J Schmidt; Veit Witzemann; Baldomero M Olivera; Joseph J McArdle
Related Documents :
6840384 - Maternal and fetal prostaglandins during acute fetal acidosis.
23461814 - First trimester papp-a mom values predictive for breech presentation at term of pregnancy.
24724224 - Value of amniotic fluid il-8 and annexin a2 in prediction of preterm delivery in preter...
647974 - Human fetal organ alkaline phosphatases.
555204 - Towards a normalization of the outcome of twin pregnancy.
7125694 - Familial benign copper deficiency.
Publication Detail:
Type:  Journal Article    
Journal Detail:
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:
Created Date:  2008-06-23     Completed Date:  2008-09-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  61-70     Citation Subset:  IM    
Affiliation:
Department of Biology, University of Utah, Salt Lake City, Utah, USA. russ_teichert@yahoo.com
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Aging / 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:
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


Previous Document:  Recent structural and mechanistic insights into endplate acetylcholine receptors.
Next Document:  Clinical phenotype of muscle-specific tyrosine kinase-antibody-positive myasthenia gravis.