Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9028075 | Chemico-Biological Interactions | 2005 | 10 Pages |
Abstract
Acute inhibition of synaptic acetylcholinesterase (AChE) is fatal to normal animals, but AChE-knockout mice (AChEâ/â) expressing normal levels of butyrylcholinesterase (BChE) could live to adulthood without AChE expression. The present study was undertaken to determine whether compensatory mechanisms occur in the mutant that allow an effective neuromuscular transmission in the chronic absence of AChE. For this we evaluated neuromuscular transmission and the distribution of nicotinic acetylcholine receptors (nAChRs) and motor nerve terminals on isolated nerve-muscle preparations from AChEâ/â mice. AChEâ/â hemidiaphragm muscles maintained at 32 °C can support muscle twitches, and tetanic contractions during intermittent nerve-stimulation over a wide range of physiological frequencies, even though they develop less force, than age-matched wild-type (AChE+/+) muscles. Tetanic fade in AChEâ/â muscles was temperature-sensitive and more marked at 22 °C than at 32 °C. Inhibition of BChE by tetraisopropylpyrophosphoramide (Iso-OMPA) intensified tetanic fade in AChEâ/â muscles, but had no effect on AChE+/+ muscles, suggesting that BChE plays a protective role in nerve terminals. Skeletal muscles from AChEâ/â mice adapted to the lack of AChE enzymatic activity by triggering a synaptic remodeling that critically occurred between the second and third week of postnatal development, during synapse elimination. In AChEâ/â muscles nAChRs distributed in a smaller and fragmented surface area, that mirrored the branching pattern of motor nerve terminals. These findings indicate that the neuromuscular system exhibits a remarkable plasticity and adaptive responses to the chronic absence of AChE activity that has important consequences for the functioning of the neuromuscular junction.
Keywords
Related Topics
Life Sciences
Environmental Science
Health, Toxicology and Mutagenesis
Authors
Emmanuelle Girard, Julien Barbier, Arnaud Chatonnet, Eric Krejci, Jordi Molgó,