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. 1975 Jan;244(2):467–495. doi: 10.1113/jphysiol.1975.sp010808

Factors affecting the time course of decay of end-plate currents: a possible cooperative action of acetylcholine on receptors at the frog neuromuscular junction.

K L Magleby, D A Terrar
PMCID: PMC1330772  PMID: 167152

Abstract

1. End-plate currents have been studied in gylcerol-treated frog sartorius nerve-muscle preparations with the voltage-clamp technique. 2. Adding the anticholinesterase prostigmine (3 muM) to the solution bathing the muscle caused a 2-7 (mean 3-3) times increase in the time constant of decay of end-plate currents. The anticholinesterase edrophonium (15 muM) also prolonged the time course of end-plate currents. 3. Pre-treatment of the preparation with collagenase, which leads to the removal of acetylcholinesterase in the synaptic cleft, prolongs the time course of end-plate currents. 4. Curare (1-2 muM), cobratoxin (0-13 muM), or alpha-bungarotoxin (0-13-0-26 muM) decreased the time constant of decay of end-plate currents in the presence of prostigmine. 5. These observations are consistant with the suggestion that repeated binding of acetylcholine (ACh) molecules to receptors as the ACh escapes from the synaptic cleft can contribute to the prolongation of end-plate currents which occurrs when acetylcholinesterase activity is eliminated. 6. Increasing the amount of transmitter released from the presynaptic nerve terminal leads to a prolongation of end-plate currents in the presence of prostigmine. 7. In the presence of prostigmine, the second of two end-plate currents (interval 2-10 msec) decays more slowly than the first. 8. ACh (1-40 muM) or carbachol (40 muM) applied in the solution bathing the muscle prolongs end-plate currents in the presence of prostigmine. 9. It is suggested on the basis of the observations described in paragraphs 6 to 8 that the time constant of decay of end-plate currents in the presence of prostigmine increases with increasing concentrations of ACh in the synaptic cleft. In the absence of prostigmine, increasing the concentration of ACh in the synaptic cleft did not change the time constant for decay of end-plate currents. 10. We interpret these results to suggest that ACh can have a cooperative action on receptors such that the association of ACh with one receptor (defined as binding a single ACh molecule) favours the binding or retention of ACh at other receptors. This implies that receptors can interact.

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Selected References

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