THE ORIGIN OF THE EFFECTS OF AN ANTICHOLINESTERASE ON THE LATENCIES OF ACTION-POTENTIALS IN MOUSE SKELETAL-MUSCLES

1 Subcutaneous injection in mice of a single dose of an organophosphor ous anticholinesterase, ecothiopate (0.5 mu mol kg(-1)), produced incr eased variability in the latency (jitter) of indirectly-elicited actio n potentials in diaphragm muscles 5 days after treatment, but there wa s no effect on the variability of latencies of endplate potentials. Th is study was designed to elucidate the mechanism(s) of the increase in action potential jitter. 2 Action potentials evoked directly by elect rical stimulation at one end of muscle fibres and recording near the o ther end had less jitter than indirectly-evoked action potentials and ecothiopate had no effect on directly-evoked action potentials. 3 In p reparations with uncut fibres, pretreatment with ecothiopate reduced b y about 20% both muscle fibre input resistance and the amplitude of sp ontaneous miniature endplate potentials. Ecothiopate had no effect on muscle fibre resting membrane potential or on the threshold potential for excitation. 4 In untreated preparations, indirectly-evoked action potentials recorded at the endplate had similar jitter to action poten tials recorded at the tendon when latencies were measured at 10% of pe ak amplitude. However, when latencies were measured at peak, there was greater jitter of action potentials at the endplate. Ecothiopate incr eased jitter of action potentials recorded at the endplate at 10% of p eak but did not significantly increase jitter of action potentials rec orded at the endplate when measured at the peak. 5 In cut-fibre prepar ations, the first endplate potential of trains was significantly incre ased after ecothiopate but there was no effect of ecothiopate on the a mplitude of plateau endplate potentials later in the train. Analysis o f plateau endplate potentials showed that 5 days after administration, ecothiopate produced an increase in the variance of endplate potentia l amplitudes and changes in the binomial parameters n and p. 6 It was concluded that the increased jitter produced by ecothiopate is not a g eneralized effect on the plasma membrane and that none of the above ob servations could explain the increased jitter. The possibility is disc ussed that increased jitter is produced by variability in times to thr eshold of endplate potentials and/or by variability in the locus of ge neration of the action potential in the perijunctional area.