Presynaptic effects of 4-aminopyridine and changes following a single giant impulse at the Torpedo...

The presynaptic changes caused by 4-aminopyridine were studied in the electric organ of Torpedo marmorata, in the resting state and during the period following transmission of a single giant discharge. Incubation with 4-aminopyridine provoked a 30-40% decrease in the density of synaptic vesicles in nerve terminals, and a similar decrease in the content of vesicular and free acetylcholine. These changes were not observed when 4-aminopyridine was applied in a low-calcium, high-magnesium solution. In the standard medium, 4-aminopyridine treated junctions were able to generate a giant electrical discharge of long duration in response to a single stimulus. During the seconds and minutes following the giant discharge, the number of synaptic vesicles was not found to be significantly altered in the whole population of nerve terminals. However, new membranous structures--looking like sacs with double membranes encircling a part of cytoplasm--were seen in approximately 25% of nerve endings; in those terminals, the number of synaptic vesicles was significantly decreased. At this stage, the junctions had not recovered their capability to generate a second giant discharge of full size and the yield of acetylcholine, adenosine 5'-triphosphate (ATP) and creatine phosphate was diminished. Thirty minutes after the single discharge, the functional recovery was achieved and the membranous sacs had disappeared; but the levels of acetylcholine, ATP and creatine phosphate were still not restored.