Stimulation‐induced factors which affect augmentation and potentiation of trasmitter release at the neuromuscular junction.

Abstract

End-plate potentials (EPP) were recorded from frog [Rana pipiens] sartorius neuromuscular junctions under conditions of decreased transmitter release to study the effect of repetitive stimulation on augmentation and potentiation of transmitter release. The magnitudes and time constants of decay of augmentation and potentiation were determined following a primary conditioning train and an identical secondary conditioning train applied from 30-170 s after the primary conditioning train. The magnitude of augmentation following the secondary conditioning trains was increased over that following the primary conditioning trains even though augmentation, with a time constant of decay of about 7 s, had decayed to insignificant levels before the onset of the secondary trains. This increase in augmentation was not due to a change in its rate of decay during the secondary trains. The increased magnitude of augmentation can be described as arising from an expression factor which, for conditioning trains of 200 impulses at 20/s, had an initial magnitude of 1.6 .+-. 1.2 (SD of observation) (the magnitude of augmentation is increased 2.6 times) and decays approximately exponentially with a time constant of 90 .+-. 50 (SD of observation) s. The expression factor decayed about 10 times slower than augmentation. Doubling the number of impulses in the primary conditioning train from 100 to 200 led to a 2.8 .+-. 1.0 (SD of observation) times increase in the magnitude of the expression factor, estimated by placing a 200 impulse secondary conditioning train 40 s after the primary conditioning train. The expression factor, while increasing the magnitude of augmentation, had little or no effect on the magnitude of potentiation or on transmitter release in the absence of augmentation. The expression factor decayed about twice as slowly as potentiation. The time constants characterizing the decay of potentiation were greater following the secondary conditioning trains than following the primary conditioning trains. The increased time constant for the decay of potentiation can be described as arising from a time constant factor which, for conditioning trains of 200 impulses at 20/s, had an initial magnitude of 1.2 .+-. 0.7 (SD of observation) (the time constant of potentiation is increased 2.2 times) and decays approximately exponentially with a time constant of 130 .+-. 45 (SD of observation) s. The time constant factor decayed about 3 times slower than potentiation. Doubling the number of impulses in the primary conditioning train from 100 to 200 led to a 1.6 .+-. 0.8 (SD of observation) times increase in the magnitude of the time constant factor, estimated by placing a 200 impulse secondary conditioning train 40 s after the primary conditioning train. The decay of potentiation following the primary conditioning train could be predicted by assuming that the rate constant for the removal of the substance responsible for potentiation is determined by a rate determining substance whose concentration and time course are reflected by the time constant factor. A 2-compartment model which could also give rise to a time constant factor was discussed. The expression factor and the time constant factor may represent changes in secondary factors (or perhaps a single secondary factor) which then affect the primary factors which directly determine the magnitude of augmentation and the time constant for the decay of potentiation. The differential effects of the expression factor and time constant factor on augmentation and potentiation suggest that some of the factors involved in augmentation and potentiation of transmitter release are different.