Factors influencing the twin-pulse facilitation of the release of transmitter at the mouse neuromuscular junction.

1. The effects of several conditions and agents on the twin-pulse facilitation of the release of transmitter at the mouse neuromuscular junction in low-Ca2+ high-Mg2+ bathing solutions were examined. 2. Twin-pulses gave two endplate potential (epps) with first (m2) and second (m2) quantal contents. The ratio of m2/m1 was taken as a measure of the degree of facilitation. 3. The mean value of this ratio was > 1. Individual ratios fluctuated widely at junctions with smaller values of m1 but were focused around 1 at junctions with larger values of m1. Thus, some populations of junctions with smaller values of m1 contributed to an increment in the mean ratio. 4. The mean ratio was virtually constant irrespective of changes in the spontaneous and evoked release of transmitter at temperatures between 20 and 36 degrees C and at external concentrations of Ca2+ from 0.4 to 0.8 mM. 5. 4-Aminopyridine(4-AP) slightly but significantly increased this ratio with increases in m1 and m2 at temperatures of 24 and 36 degrees C. Ouabain slightly but significantly reduced the ratio, with increases in m1 and m2. The steadiness of the ratio was maintained in the presence of caffeine, high K+, neomycin or omega-conotoxin irrespective of changes in m1 and m2, except in the case of omega-conotoxin. 6. Spontaneous output at 36 degrees C increased in the presence of 4-aminopyridine, ouabain, caffeine, high K+ or neomycin. 7. These results indicate that maintenance of a stable value of the ratio of m2 to m1 is a dominant feature.(ABSTRACT TRUNCATED AT 250 WORDS)