CONTROL OF THE CALCIUM-CONCENTRATION INVOLVED IN ACETYLCHOLINE-RELEASE AND ITS FACILITATION - AN ADDITIONAL ROLE FOR SYNAPTIC VESICLES

2,5-Diterbutyl-1,4-benzohydroquinone, a specific blocker of Ca2+-ATPas e pumps, increased acetylcholine release from an identified synapse of Aplysia, as well as from Torpedo and mouse caudate nucleus synaptosom es. Because 2,5-diterbutyl-1,4-benzohydroquinone does not change the p resynaptic Ca2+ influx, the enhancement of acetylcholine release could be due to an accumulation of Ca2+ in the terminal. This possibility w as further checked by studying the effects of 2,5-diterbutyl-1,4-benzo hydroquinone on twin pulse facilitation, classically attributed to res idual Ca2+. While preventing the fast sequestration of Ca2+ by presyna ptic organelles, 2,5-diterbutyl-1,4-benzohydroquinone magnified both t win pulse facilitation observed under low extracellular Ca2+ concentra tion and twin pulse dysfacilitation observed under high extracellular Ca2+ concentration. Thus, it is concluded that 2,5-diterbutyl-1,4-benz ohydroquinone, by preventing Ca2+ buffering near transmitter release s ites, modulates acetylcholine release. As 2,5-diterbutyl-1,4-benzohydr oquinone was also shown to decrease by 50% the uptake of Ca-45(2+) by isolated synaptic vesicles, we propose that synaptic vesicles can cont rol the presynaptic Ca2+ concentration triggering the release of neuro transmitter. (C) 1998 IBRO. Published by Elsevier Science Ltd.