End plate currents (EPCs) were recorded from the glycerol treated frog sartorius nerve muscle preparation under voltage clamp. Prostigmin, edrophonium, or pretreatment with collagenase (removes acetylcholine (ACh) esterase) increased the time constant of decay of EPCs several times. In the presence of prostigmin adding curare, cobra toxin, or waiting for significant desensitization with bath applied ACh decreased the time constant of decay of EPCs. These results suggest that in prostigmin EPCs are prolonged because an appreciable fraction of release ACh is bound to receptors leading to a delay in diffusion from the cleft. In prostigmin increasing the amount of ACh released from the nerve terminal (by using the properties of facilitation and depression during repetitive nerve stimulation) led to an increase in the time constant of decay of EPCs and bath applied ACh (1-40 μM) or 40 μM carbachol also increased the time constant of decay of nerve evoked EPCs. Changes in quantal release or bath applied ACh or carbachol had negligible effect on the time course of EPCs in the absence of prostigmin when hydrolysis determines the rate of removal of ACh. These results suggest a cooperative action of ACh; the association of ACh with one binding site favors the binding or retention of ACh at other sites. Increasing cleft [ACh] would then lead to increased binding or retention of ACh and further delay its diffusion from the cleft.
|Original language||English (US)|
|Pages (from-to)||No. 1400|
|Issue number||5 II|
|State||Published - Jan 1 1974|
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