Fatigability of rat hindlimb muscles after acute irreversible acetylcholinesterase inhibition

The purpose of this study was to investigate the functional impact of acute irreversible inhibition of acetylcholinesterase (AChE) on the fatigability of medial gastrocnemius and plantaris muscles of Sprague-Dawley rats. Afte r treatment with methanesulfonyl fluoride (a lipid-soluble anticholinestera se), which reduced their AChE activity by >90%, these muscles were subjecte d to an in situ indirect stimulation protocol, including a series of isolat ed twitch and tetanic contractions preceding a 3-min fatigue regimen (100-m s trains at 75 Hz applied every 1.5 s). During the first minute of the fati gue regimen, the effects of AChE inhibition were already near maximal, incl uding marked reductions in peak tension and the force-time integral (area), as well as a decrement of compound muscle action potential amplitudes with in a stimulus train. Neuromuscular transmission failure was the major contr ibutor of the force decreases in the AChE-inhibited muscles. However, despi te this neuromuscular transmission failure, muscles of which all AChE molec ular forms were nearly completely inhibited were still able to function, al though abnormally, during 3 min of intermittent high-frequency nerve stimul ation.