Electrophysiological and Ultrastructural Characterization of Neuromuscular Junctions in Diaphragm Muscle of Acetylcholinesterase Knockout Mice

Abstract

14. ABSTRACT Electrophysiological and ultrastructural studies were performed on phrenic nerve-hemidiaphragm preparations isolated from wild-type (AChE +/+) and acetylcholinesterase knockout (AChE -/-) mice to determine the compensatory mechanism manifested by the neuromuscular junction to excess acetylcholine (ACh). Nerve-elicited muscle contractions, miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) were recorded by conventional electrophysiological techniques from phrenic nerve-hemidiaphragm preparations isolated from 1.5- to 2-month-old mice. 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 in AChE -/- diaphragms showed a slight reduction in amplitude (20%) and a small prolongation in decay (26%) relative to values observed in wild-type mice. In contrast, MEPPs recorded from AChE +/+ diaphragms exposed for 30 min to the selective AChE inhibitor 5-bis(4-allyldimethyl-ammoniumphenyl)pentane-3-one (BW284C51) exhibited a pronounced increase in amplitude (63%) and a marked prolongation in decay (115%). The difference between MEPP amplitudes and decays in AChE -/- diaphragms and in AChE +/+ diaphragms treated with BW284C51 represents effective adaptation by the former to a high ACh environment. Electron microscopic examination revealed that diaphragm muscles of AChE -/- mice had smaller nerve terminals and diminished pre- and postsynaptic surface contacts relative to neuromuscular junctions of AChE +/+ mice. The morphological changes are suggested to account, in part, for the ability of muscle from AChE -/- mice to function in the complete absence of AChEn.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2008
Accession Number
ADA502010

Entities

People

  • Ellen Duysen
  • Michael Adler
  • Oksana Lockridge
  • Sharad S. Deshpande
  • Tracey A. Hamilton

Organizations

  • United States Army Medical Research Institute of Chemical Defense

Tags

DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Amplitude
  • Biological Sciences
  • Cells
  • Electron Microscopy
  • Electrons
  • Frequency
  • Inhibitors
  • Microscopy
  • Muscles
  • Nerve Agents
  • Neuromuscular Transmission
  • Peripheral Nervous System
  • Phrenic Nerves
  • Skeletal Muscle
  • Synapses
  • Tissues

Fields of Study

  • Medicine

Readers

  • Cardiovascular Physiology
  • Neurotoxicology

Technology Areas

  • Microelectronics
  • Microelectronics - Microelectromechanical Systems