title: Activation and desensitisation of acetylcholine release by zinc at Torpedo nerve terminals.
abstract: Treatment with 100 or 250 microM ZnCl2 irreversibly blocked neurotransmission in the Torpedo electric organ by inhibiting acetylcholine (ACh) release. In Zn2+-treated tissue, release failure did not result from impairment of Ca2+ entry since stimulation still provoked an accumulation of Ca2+. Also pretreatment of isolated synaptosomes with Zn2+ inhibited to the same extent the release elicited by KCl-evoked depolarisation and the release elicited by using the Ca2+ ionophore A23187. On the other hand, after application of A23187, Zn2+ by itself efficiently triggered ACh release from synaptosomes. This dual effect of Zn2+ was also observed to occur in proteoliposomes equipped with mediatophore (a protein of the presynaptic membrane characterised by its capability to support Ca2+-dependent transmitter release). Hence, Zn2+ mimicked two fundamental actions of Ca2+ on nerve terminals, which are: (1) the immediate activation of release, and (2) a more slowly developing desensitisation of release. Zn2+ was more powerful than Ca2+ for both actions. It is concluded that the dual action of Zn2+ on the mediatophore protein accounts at least in part for its complex effects on neurotransmission.
authors.affiliation: Département de pharmacologie, CMU, CH-1211 Geneva 4, Switzerland.
authors.forename: Y
authors.initials: Y
authors.lastname: Dunant
authors.forename: F
authors.initials: F
authors.lastname: Loctin
authors.forename: J P
authors.initials: JP
authors.lastname: Vallée
authors.forename: A
authors.initials: A
authors.lastname: Parducz
authors.forename: B
authors.initials: B
authors.lastname: Lesbats
authors.forename: M
authors.initials: M
authors.lastname: Israël
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism; D004557:Electric Organ / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D011189:Potassium Chloride; D011510:Proteolipids / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014101:Torpedo; D015032:Zinc / Q000494:pharmacology*
chemical_list: D011510:Proteolipids; C020485:proteoliposomes; D000001:Calcimycin; D011189:Potassium Chloride; D015032:Zinc; D000109:Acetylcholine; D002118:Calcium