The Mechanism of Neuromuscular Fatigue: A Study of Mammalian Muscle Using Excitation-Contraction Uncoupling

Neuromuscular transmission failure was measured during rapid repetitive stimulation of the rat hemidiaphragm in vitro.after excitation-contraction uncoupling by hyperosmolar glycerol, washing, and dantrolene sodium. Observations of resting membrane, miniature endplate, action, and endplate potentials (epps) showed that neuromuscular transmission failure occurred during stimulation because of a decrement of the epp. This decrement was due both to a reduced number of quanta released and to a variable reduction of quantal size. The time course of these events was studied, and limited observations were made on recovery. Observations of the difference between the epp decrement of cut muscle and of partially curarized muscle suggest a prejunctional action of curare.