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

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-bis(4-allyldimethyl-ammoniumphenyl)pentane-3-one (BW284C51) exhibited a pronounced increase in amplitude (42%) and a more marked prolongation in decay (76%).

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2011
Accession Number
ADA561712

Entities

People

  • Angela L. Purcell
  • Ellen G. Duysen
  • Michael Adler
  • Oksana Lockridge
  • Richard E. Sweeney
  • Sharad S. Deshpande
  • Tracey A. Hamilton

Organizations

  • United States Army Medical Research Institute of Chemical Defense

Tags

DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Alzheimer Disease
  • Biomedical Research
  • Cells
  • Data Analysis
  • Electron Microscopes
  • Electron Microscopy
  • Enzymes
  • Microscopy
  • Muscle Fibers
  • Muscles
  • Nerve Agents
  • Neuromuscular Transmission
  • Peripheral Nervous System
  • Phrenic Nerves
  • Skeletal Muscle
  • Synapses

Fields of Study

  • Medicine

Readers

  • Exercise and Sports Science.
  • Immunology
  • Neurotoxicology