Accession Number:

ADA561712

Title:

Role of Acetylcholinesterase on the Structure and Function of Cholinergic Synapses: Insights Gained from Studies on Knockout Mice

Descriptive Note:

Journal article

Corporate Author:

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD

Report Date:

2011-01-01

Pagination or Media Count:

13.0

Abstract:

Electrophysiological and ultrastructural studies were performed on phrenic nerve-hemidiaphragm preparations isolated from wild-type and acetylcholinesterase AChE knockout KO mice to determine the compensatory mechanisms manifested by the neuromuscular junction to excess acetylcholine ACh. The diaphragm was selected since it is the primary muscle of respiration, and it must adapt to allow for survival of the organism in the absence of AChE. Nerve-elicited muscle contractions, miniature endplate potentials MEPPs and evoked endplate potentials EPPs were recorded by conventional electrophysiological techniques from phrenic nervehemidiaphragm preparations isolated from 1.5- to 2-monthold wild-type AChE or AChE KO AChE-- mice. These recordings were chosen to provide a comprehensive assessment of functional alterations of the diaphragm muscle resulting from the absence of AChE. Tension measurements from AChE-- mice revealed that the amplitude of twitch tensions was potentiated, but tetanic tensions underwent a use-dependent decline at frequencies below 70 Hz and above 100 Hz. MEPPs recorded from hemidiaphragms of AChE-- mice showed a reduction in frequency and a prolongation in decay 37 but no change in amplitude compared to values observed in agematched wild-type littermates. In contrast, MEPPs recorded from hemidiaphragms of wild-type mice that were exposed for 30 min to the selective AChE inhibitor 5-bis4-allyldimethyl-ammoniumphenylpentane-3-one BW284C51 exhibited a pronounced increase in amplitude 42 and a more marked prolongation in decay 76.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE