Miniature endplate current kinetics at the mouse neuromuscular junction: Effects of temperature and medium viscosity

The time course of miniature endplate currents (MEPCs), derived by extracellular focal recording, was studied in the mouse neuromuscular junction at different temperatures and medium viscosities, and in eserine-treated endplates. At low temperatures (6-10°C), almost the whole MEPC decay is exponential and the rising phase is not significantly modified by the channel closing process. At physiological temperatures (38-40°C), the early part of the decay is much slower than the later part and the rising phase is made shorter and smaller by channel closing, showing that the channel opening and channel closing processes overlap remarkably. Even at physiological temperatures, however, the late part of MEPC decay shows an exponential time course. At high temperatures the channel opening process has low temperature sensitivity and slows down when bath solution viscosity is increased, suggesting that at high temperatures channel opening kinetics may mainly be controlled by the time course of acetylcholine diffusion. The lower limit of conformational change rate leading to channel opening was estimated at 10°C (4400 s^-1). Experimentally recorded MEPCs were mathematically simulated to obtain a quantitative description of the processes controlling MEPC generation. Mathematical simulation further suggests that (i) acetylcholine diffusion kinetics may affect the onset rate of MEPCs without, however, being rate-limiting; and (ii) partial, transient acetylcholinesterase inhibition operated by acetylcholine may explain the low temperature sensitivity exhibited by the onset rate of MEPCs at high temperatures.