Miniature endplate currents of muscle fibers from rat diaphragm during galantamine-induced acetylcholinesterase inhibition

Miniature endplate currents (MEPC) were recorded in muscle fibers of rat diaphragm using voltage clamp technique during acetylcholinesterase (AChE) inhibition induced by various concentrations of galantamine. Their amplitude and time course began to increase at a galantamine concentration of 3.16·10−8 g/ml. Increased concentrations of galantamine produced a greater effect. Maximum amplitude and time course were reached at a concentration of 10−6 g/ml. The input resistance of muscle fibers increased under the effects of galantamine. In all cases MEPC fell exponentially. At a concentration of 10−5 g/ml galantamine produced a curarelike effect; amplitude and time course of decay increased to a lesser extent than at a concentration of 10−6 and the decay in MEPC became biphasic. Following washout of galantamine (10−5 g/ml) the time course of MEPC first rose, then fell, returning to the initial level in 3 h, and decay again became exponential. Changes in MEPC parameters under the effects of different concentrations of galantamine and washout were closely correlated. A positive correlation was found between the time course of decay and MEPC amplitude both in the presence and absence of AChE inhibition. It is postulated that the functional importance of synaptic AChE in repressing the postsynaptic action of acetylcholine is limited and that parameters of postsynaptic response may therefore be used to evaluate its action.