The number of acetylcholine molecules in a quantum and the interaction between quanta at the subsynaptic membrane of the skeletal neuromuscular synapse.
1. Postsynaptic responses to acetylcholine released from nerve terminals and from iontophoretic micropipettes were investigated in skeletal twitch-muscle fibers of the snake. The preparation consists of thin sheets of muscle fibers in which details of the end plate, including the outlines of individual synaptic boutons, are clearly seen in the living state. After treatment with collagenase, the motor nerve and its terminal boutons can be removed to expose the intact subsynaptic membrane to direct application of ACh by iontophoretic pipettes. 2. The number of ACh molecules in a quanta was estimated to be fewer than 10,000. This was done by developing a sensitive bioassay to measure the output of ACh from iontophoretic pipettes needed to produce synaptic responses closely resembling nerve-released miniature postsynaptic potentials. 3. Postsynaptic receptors are not saturated by the ACh in a quantum, since the peak of the quantal response produced by an appropriate background concentration of ACh from a pipette. 4. When acetylcholine esterase is inhibited, two or more quanta can act upon partially overlapping postsynaptic membrane areas and potentiate each other's effects. This potentiation reveals itself as a prolongation of the synaptic current. Postsynaptic potentiation is a consequence of the nonlinear dose-response characteristics of ACh receptors and can also be demonstrated in a model system in which ACh micropipettes substitute for quantal release from the nerve. 5. With AChE fully active, however, each quantum is functionally isolated from its neighbors and no postsynaptic potentiation is seen. 6. It is suggested that postsynaptic potentiation between quantum may play a role in signaling at synapses which have nonlinear dose-response characteristics and where transmitter is not so rapidly inactivated as at the neuromuscular synapse.
D000109:Acetylcholine / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials; D007531:Isoflurophate; D008274:Magnesium / Q000494:pharmacology; D009045:Motor Endplate / Q000187:drug effects / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D011955:Receptors, Drug; D012911:Snakes; D013268:Stimulation, Chemical; D013570:Synaptic Membranes / Q000187:drug effects
D011955:Receptors, Drug; D007531:Isoflurophate; D000110:Acetylcholinesterase; D008274:Magnesium; D000109:Acetylcholine; D002118:Calcium