Effect of phasic activation on endplate potential in rat diaphragm

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.