Document Detail


Reduced acetylcholine receptor density, morphological remodeling, and butyrylcholinesterase activity can sustain muscle function in acetylcholinesterase knockout mice.
MedLine Citation:
PMID:  15318343     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nerve-evoked contractions were studied in vitro in phrenic nerve-hemidiaphragm preparations from strain 129X1 acetylcholinesterase knockout (AChE-/-) mice and their wild-type littermates (AChE+/+). The AChE-/- mice fail to express AChE but have normal levels of butyrylcholinesterase (BChE) and can survive into adulthood. Twitch tensions elicited in diaphragms of AChE-/- mice by single supramaximal stimuli had larger amplitudes and slower rise and decay times than did those in wild-type animals. In AChE-/- preparations, repetitive stimulation at frequencies of 20 and 50 Hz and at 200 and 400 Hz produced decremental muscle tensions; however, stimulation at 70 and 100 Hz resulted in little or no loss of tension during trains. Muscles from AChE+/+ mice maintained tension at all frequencies examined but exhibited tetanic fade after exposure to the selective AChE inhibitor 1,5-bis(4-allyldimethyl-ammoniumphenyl)pentane-3-one (BW 284C51). The ability of diaphragm muscles from AChE-/- mice to maintain tension at 70 and 100 Hz suggests a partial compensation for impairment of acetylcholine (ACh) hydrolysis. Three mechanisms--including a reliance on BChE activity for termination of ACh action, downregulation of nicotinic acetylcholine receptors (nAChRs), and morphological remodeling of the endplate region--were identified. Studies of neuromuscular transmission in this model system provide an excellent opportunity to evaluate the role of AChE without complications arising from use of inhibitors.
Authors:
Michael Adler; Heather A Manley; Angela L Purcell; Sharad S Deshpande; Tracey A Hamilton; Robert K Kan; George Oyler; Oksana Lockridge; Ellen G Duysen; Robert E Sheridan
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Muscle & nerve     Volume:  30     ISSN:  0148-639X     ISO Abbreviation:  Muscle Nerve     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-19     Completed Date:  2004-09-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7803146     Medline TA:  Muscle Nerve     Country:  United States    
Other Details:
Languages:  eng     Pagination:  317-27     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Wiley Periodicals, Inc.
Affiliation:
Neurotoxicology Branch, Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010, USA. Michael.Adler@amedd.army.mil
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / metabolism
Acetylcholinesterase / deficiency*,  genetics
Animals
Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide / pharmacology
Butyrylcholinesterase / metabolism*,  physiology
Diaphragm / drug effects,  enzymology*,  ultrastructure
Enzyme Activation / genetics
Female
Hydrolysis
Male
Mice
Mice, Knockout
Muscle Contraction / drug effects,  physiology*
Receptors, Nicotinic / metabolism*,  ultrastructure
Chemical
Reg. No./Substance:
0/Receptors, Nicotinic; 402-40-4/Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide; 51-84-3/Acetylcholine; EC 3.1.1.-/Butyrylcholinesterase; EC 3.1.1.7/Acetylcholinesterase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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