Neuromuscular junction endplate potentials (EPPs) decrease quickly and to a
targe extent during continuous stimulation. The present study examined the
hypothesis that EPP rundown recovers rapidly, thereby substantially preser
ving neurotransmission during intermittent compared with continuous stimula
tion. Studies were performed in vitro on rat diaphragm, using mu-conotoxin
to allow recording of normal-sized EPPs from intact fibers. During continuo
us 5- to 100-Hz stimulation, EPP amplitude declined with a biphasic time co
urse. The initial fast rate of decline was modulated substantially by stimu
lation frequency, whereas the subsequent slow rate of decline was relativel
y frequency independent. During intermittent 5- to 100-Hz stimulation (duty
cycle 0.33), EPP amplitude declined rapidly during each train, but recover
ed substantially by the onset of the following train. The intra-train decli
nes were substantially greater than the inter-train declines in EPP amplitu
de. Intra-train reductions in EPP amplitude were stimulation frequency depe
ndent, based on both the total decline and rate constant of EPP decline. In
contrast, the degree of recovery from train to train was independent of st
imulation frequency, indicating low frequency dependence of inter-train run
down. The substantial recovery of EPP amplitude in between trains resulted
in greater cumulative EPP size during intermittent compared with continuous
stimulation. During continuous stimulation, EPP drop-out was only seen dur
ing 100-Hz stimulation; this was completed mitigated during intermittent st
imulation. Miniature EPP size was unaffected by either continuous or interm
ittent stimulation. The pattern of rapid intra-train rundown and slow inter
-train rundown of EPP size during intermittent stimulation is therefore due
to rapid changes in the magnitude of neurotransmitter release rather than
to axonal block or postsynaptic receptor desensitization. These findings in
dicate considerable rundown of EPP amplitudes within a stimulus train, with
near complete recovery by the onset of the next train. This substantially
attenuates the decrement in EPP amplitude during intermittent compared with
continuous stimulation, thereby preserving the integrity of neurotransmiss
ion during phasic activation.