Résumé :
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Communication n° 384 Introduction. Although AChE knockout mice survive they have abnormal locomotor activity. Because most cholinesterase inhibitors show little selectivity between acetylcholinesterase (AChE) and butyrylcholinesterase, it is difficult to establish the role of AChE in neuromuscular function Objectives. Evaluate hindlimb neuromuscular function in AChE knockout mice (AChE-/-). Methods. Muscle isometric contractile properties of Tibialis anterior muscle in response to electric nerve stimulation were measured in situ in AChE-/- and wild-type mice. Results. The maximum twitch force in response to a single nerve stimulation was higher in AChE-/- versus wild-type mice (>2x; p<0.05). After repetitive nerve stimulation (25 Hz, 500 ms), submaximal tetanic force was also higher in AChE-/- mice (p<0.05). In contrast, maximal tetanic force (> 50Hz) was unchanged (p>0.05) but tension rapidly decreased over time (500 ms) during the tetanic contraction (tetanic fade). This tetanic fade was partially blocked by direct stimulation of the muscle (p<0.05). During repeated submaximal tetanic contractions (25Hz, 500 ms, 1 contraction/s), force decreased more rapidly in AChE-/-mice, after the first contraction. Conclusions. Some important aspects of neuromuscular function were altered in AChE-/- mice. The most stricking changes observed in AChE-/- mice is rapid fatigue to sustained or repetitive muscle contraction. However, maximal production of force is unchanged Our study verifies that AChE plays an important role in neuromuscular response to sustained stimuli. However, despite reduced, neuromuscular transmission is possible in the absence of AChE.
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