Activation and desensitisation of acetylcholine release by zinc at Torpedo nerve terminals.
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.
Dunant
Y
Y
Département de pharmacologie, CMU, CH-1211 Geneva 4, Switzerland.
Loctin
F
F
Vallée
J P
JP
Parducz
A
A
Lesbats
B
B
Israël
M
M
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*
D011510:Proteolipids; C020485:proteoliposomes; D000001:Calcimycin; D011189:Potassium Chloride; D015032:Zinc; D000109:Acetylcholine; D002118:Calcium