MINIATURE END-PLATE CURRENT KINETICS AT THE MOUSE NEUROMUSCULAR-JUNCTION - EFFECTS OF TEMPERATURE AND MEDIUM VISCOSITY

The time course of miniature endplate currents (MEPCs), derived by ext racellular focal recording, was studied in the mouse neuromuscular jun ction at different temperatures and medium viscosities, and in eserine -treated endplates. At low temperatures (6-10 degrees C), almost the w hole MEPC decay is exponential and the rising phase is not significant ly modified by the channel closing process. At physiological temperatu res (38-40 degrees C), the early part of the decay is much slower than the later part and the rising phase is made shorter and smaller by ch annel closing, showing that the channel opening and channel closing pr ocesses overlap remarkably. Even at physiological temperatures, howeve r, the late part of MEPC decay shows an exponential time course. At hi gh temperatures the channel opening process has low temperature sensit ivity and slows down when bath solution viscosity is increased, sugges ting that at high temperatures channel opening kinetics may mainly be controlled by the time course of acetylcholine diffusion. The lower li mit of conformational change rate leading to channel opening was estim ated at 10 degrees C (4400 s(-1)). Experimentally recorded MEPCs were mathematically simulated to obtain a quantitative description of the p rocesses controlling MEPC generation. Mathematical simulation further suggests that (i) acetylcholine diffusion kinetics may affect the onse t rate of MEPCs without, however, being rate-limiting; and (ii) partia l, transient acetylcholinesterase inhibition operated by acetylcholine may explain the low temperature sensitivity exhibited by the onset ra te of MEPCs at high temperatures.