Release of ATP from stimulated nerve electroplaque junctions.

Abstract

THREE successive phases can be distinguished when the amplitude of the electrophysiological response of Torpedo electroplaques is recorded during stimulation at 5 or 10 Hz (ref. 1). A decrease, lasting about 30 s, is followed by a plateau of about 30 s during which the amplitude is maintained at 30–40% of its initial value. After the plateau, a late decrease brings the response to negligible levels in a few minutes. These three phases are correlated with variations in the tissue level of total acetylcholine (ACh)—the amount of transmitter decreasing during the first phase, increasing to control levels during the plateau and declining again. These variations are about 30–40% of the total level of ACh. No change is observed when only the pool of bound ACh is measured2,3. In Torpedo homogenates, bound ACh (protected from hydrolysis by esterases3) is associated with a population of synaptic vesicles, which have been isolated by fractionation techniques4. It has been shown that ATP is present in the vesicular fraction5. When Torpedo electric organ tissue is stimulated more than would be necessary to exhaust the electrophysiological response, or when for some other reason synthesis of new transmitter is rendered inefficient, a decrease in bound or vesicular ACh is observed. Of all the variations in ACh described, only the decline in bound ACh has been thoroughly investigated and confirmed by other laboratories6. It is known from fractionation experiments that both ATP and ACh are associated with synaptic vesicles, and a decrease in the vesicular content of the two substances was found in the experimental conditions that produce a decline in the pool of bound ACh (ref. 6). Several authors have collected ATP in the perfusate from stimulated neuromuscular junctions7–9, but the nucleotide was not found in perfusates from stimulated autonomic ganglia10.