The rate-limiting steps of the rising phase of miniature end plate currents in the mouse diaphragm

To gain insight about the processes controlling the opening rate of postsynaptic channels following the release of a quantum of acetylcholine, the onset rate of miniature end plate currents (MEPCs) was evaluated at different temperatures and in a high viscosity medium.The onset rate of MEPCs, measured as the rise time from 10% to 50% of the peak amplitude, is remarkably sensitive to temperature in the range from 9° C to about 19° C, while it is almost constant at higher temperatures (from 20 to 39° C).The viscosity of the medium affects the onset rate of MEPCs significantly: when 10% Dextran is added to the bath solution, the rise time is slowed down by about 20%.The present results suggest that at high temperatures (above about 19 °C) the rate of the rising phase of MEPCs is limited only by the rate of acetylcholine diffusion; at low temperatures (below about 19° C), the binding of neurotransmitter and/or the subsequent protein conformational change leading to opening of the acetylcholine channel become so slow as to reduce greatly the onset rate of MEPCs.The relative contribution of these three processes to the overall kinetics of the rising phase of MEPCs is not investigated here.