Abstract

In the sartorius muscle of the frog, diisopropylfluorophosphate (DFP), an irreversible inhibitor of cholinesterase, reduced the amplitude, shortened the time course (50%) and shifted the equilibrium potential of the end-plate current (EPC) to more negative values. Under control conditions, the half decay time of the EPC is potential-dependent; in the presence of DFP it became much less so. Removal of the excess DFP by washing the muscles in normal Ringer's resulted in partial recovery of the EPC amplitude and a 2-fold increase in the half decay time. When tetanic stimulation was applied (25 Hz) in the presence of DFP and also after washing, the first five EPCS were augmented and subsequent EPCs gradually declined in amplitude by about 60%. After treatment for 30 minutes with pyridine-2-aldoxime methiodide to dephosphorylate the inhibited sites, and after washing, the EPC amplitude and the half decay time were restored almost to control values. In the presence of DFP the decay of the EPC followed a two-step exponential function; after washing the preparation prior to pyridine-2-aldoxime methiodide treatment it returned to a one-step exponential function similar to control but with a much larger time constant. At the concentration used, DFP did not affect the membrane potential or spike activity. It is proposed that DFP acts on both cholinesterase and the ionic conductance modulator for the EPC and that the interaction of acetylcholine with its receptor sites has a much faster time course than that of the resultant conformational changes in the ionic conductance modulator.