Post-synaptic potentiation: interaction between quanta of acetylcholine at the skeletal neuromuscular synapse.

1. Post-synaptic responses to acetylcholine (ACh) released from nerve terminals and from iontophoretic micropipettes were investigated in skeletal muscle fibres of the snake. Each fibre has a compact end-plate consisting of fifty to seventy synaptic boutons. The fibres were voltage clamped, and synaptic currents were recorded from visually identified end-plates. 2. When acetylcholinesterase (AChE) is inhibited, a potentiating interaction is observed between two or more quanta that are released close to each other from a synaptic bouton and act upon partially overlapping postsynaptic areas. The potentiation is expressed as a prolongation of the synaptic current. This potentiation also occurs under normal conditions of release when about 300 quanta are distributed over the entire end-plate, so thet the presynaptic release sites are separated by an average of 2 mum. An analogous potentiating interaction is observed when micropipettes, closely apposed to the subsynaptic membrane, substitute for quantal release sites. ACh from one pipette potentiates the response to ACh from another pipette less than 2 mum away. 3. In contrast, with AChE fully active no post-synaptic potentiation is seen when the normal complement of quanta is released over the entire end-plate. The time course of the synaptic currents in response to a single quantum or to 300 quanta is similar. It is concluded that functionally the quanta act independently of each other, because AChE isolates each quantum from its neighbours by limiting the lifetime of ACh and its lateral diffusion in the synaptic cleft. The estimated area over which a quantum normally acts is less than 2mum2. 4. Post-synaptic receptors are not saturated by the ACh in a quantum, since the peak of the quantal response adds linearly to the response produced by an appropriate background concentration of ACh from a pipette. This conclusion is supported by the observation that upon inhibition of AChE the peak amplitude of the quantal current response increases by about 20% with no change in its time to peak. 5. It is suggested that post-synaptic potentiation between quanta may play a role in signalling at synapses in which non-linear dose-response characteristics have been observed and where transmitter is not as repidly inactivated as the neuromuscular synapse.