Multiple actions of zinc on transmitter release at mouse end-plates.
In mouse diaphragm, the increase in frequency of mini end-plate potentials (fmepp), by Ca2+ or Ba2+ in 20 mM K+, was reversibly inhibited by Zn2+ in a manner consistent with competition between Zn2+ and Ca2+ at a site which interacts with only one atom of Zn with an apparent dissociation constant (Ki) of about 0.015 mM. Between 0.5 mM and 2 mM, Zn2+ caused a rapid and reversible dose-dependent increase in fmepp in 20 mM K+/0 Ca2+. Prolonged or repeated exposure to Zn2+ produced a slow increase in fmepp followed by a decline, which once started, was not modified by of Zn2+. The time course was prolonged in raised Mg2+, bekanamycin, or in 5 mM K+ solution, and graded with Zn2+ concentration, but total numbers of MEPPs induced by 0.1 mM, 1 mM or 4 mM Zn2+ were not significantly different. When fmeppp fell it became insensitive to Ca2+, Ba2+, La3+ (in 20 mM K+), ethanol and raised osmotic pressure. Before complete block of responses to Ca2+, the Ca2+/fmepp dose/response curve in 20 mM K+ was shifted to the right. These results indicate that Zn2+ enters the terminal via voltage-gated Ca2+ channels that interact in a complex way with these ions and then acts (a) as a partial agonist at sites where Ca2+ normally governs transmitter release, and (b) to produce irreversible changes in the nerve terminal, associated with a rise and subsequent fall of fmepp and loss of sensitivity of the release mechanism to Ca2+ and other agents.
Wang
Y X
YX
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia Vancouver, Canada.
Quastel
D M
DM
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007425:Intracellular Membranes / Q000378:metabolism; D008433:Mathematics; D051379:Mice; D009045:Motor Endplate / Q000378:metabolism* / Q000502:physiology; D009469:Neuromuscular Junction / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology*
D018377:Neurotransmitter Agents; D015032:Zinc; D002118:Calcium