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+-ATPase pumps, increased acetylcholine release from an identified synapse of Aplysia, as well as from Torpedo and mouse caudate nucleus synaptosomes. Because 2,5-diterbutyl-1,4-benzohydroquinone does not change the presynaptic Ca2+ influx, the enhancement of acetylcholine release could be due to an accumulation of Ca2+ in the terminal. This possibility was further checked by studying the effects of 2,5-diterbutyl-1,4-benzohydroquinone on twin pulse facilitation, classically attributed to residual Ca2+. While preventing the fast sequestration of Ca2+ by presynaptic organelles, 2,5-diterbutyl-1,4-benzohydroquinone magnified both twin pulse facilitation observed under low extracellular Ca2+ concentration and twin pulse dysfacilitation observed under high extracellular Ca2+ concentration. Thus, it is concluded that 2,5-diterbutyl-1,4-benzohydroquinone, by preventing Ca2+ buffering near transmitter release sites, modulates acetylcholine release. As 2,5-diterbutyl-1,4-benzohydroquinone was also shown to decrease by 50% the uptake of 45Ca2+ by isolated synaptic vesicles, we propose that synaptic vesicles can control the presynaptic Ca2+ concentration triggering the release of neurotransmitter.
Fossier
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Laboratoire de Neurobiologie Cellulaire et Moléculaire, C.N.R.S., Gif sur Yvette, France.
Diebler
M F
MF
Mothet
J P
JP
Israel
M
M
Tauc
L
L
Baux
G
G
D000109:Acetylcholine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002799:Cholinergic Fibers / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006873:Hydroquinones / Q000494:pharmacology; D051379:Mice; D009411:Nerve Endings / Q000378:metabolism; D009994:Osmolar Concentration; D009435:Synaptic Transmission / Q000187:drug effects; D013572:Synaptic Vesicles / Q000378:metabolism / Q000502:physiology*; D014101:Torpedo
D004791:Enzyme Inhibitors; D006873:Hydroquinones; C019359:2,5-di-tert-butylhydroquinone; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D000109:Acetylcholine; D002118:Calcium