Acetylcholine receptor site density affects the rising phase of miniature endplate currents.

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Abstract
The relationship between acetylcholine receptor (AcChoR) site density (.sigma.) and the rising phase of the miniature endplate current was determined in esterase-inactivated lizard [ANOLIS-CAROLINENSIS] intercostal neuromuscular junctions. The currents were recorded by using a voltage clamp. The receptor site density was determined by EM autoradiography after labeling with 125I-labeled .alpha.-bungarotoxin in normal endplates and in those partially inactivated with nonradioactive .alpha.-bungarotoxin. As .sigma. was decreased the rise time increased and the amplitude decreased. The saturating disk model, which implies a quantum of acetylcholine (AcCho) acts on a small postsynaptic area at saturating concentration is compatible. In the normal neuromuscular junction the most likely number of AcCho molecules needed to open an ion channel apparently is 2 and the 20-80% rise time of < 100 .mu.s is influenced by the .sigma.-dependent factors, e.g., diffusion and binding of AcCho to AcChoR, and the .sigma.-independent time delays, e.g., the conformation change time to open the ion channels. The lower limits to the forward rate constant of AcCho binding to AcChoR are .gtoreq. 3 .times. 107 M-1 s-1, and the diffusion constant for AcCho in the cleft is .gtoreq. 4 .times. 10-6 cm2/s.