Wang Y X, Quastel D M
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia Vancouver, Canada.
Pflugers Arch. 1990 Feb;415(5):582-7. doi: 10.1007/BF02583509.
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.
在小鼠膈肌中，在20 mM钾离子存在的情况下，钙离子或钡离子使微小终板电位（fmepp）频率增加，而锌离子以一种与锌离子和钙离子在一个仅与一个锌原子相互作用的位点上竞争相一致的方式可逆地抑制这种增加，其表观解离常数（Ki）约为0.015 mM。在0.5 mM至2 mM之间，锌离子在20 mM钾离子/无钙离子的情况下导致fmepp快速且可逆的剂量依赖性增加。长时间或反复暴露于锌离子会使fmepp缓慢增加，随后下降，一旦开始下降，就不会因锌离子的作用而改变。在升高的镁离子、贝那霉素或5 mM钾离子溶液中，时间进程会延长，并与锌离子浓度成梯度变化，但0.1 mM、1 mM或4 mM锌离子诱导的微小终板电位（MEPPs）总数没有显著差异。当fmepp下降时，它对钙离子、钡离子、镧离子（在20 mM钾离子中）、乙醇和渗透压升高变得不敏感。在对钙离子的反应完全阻断之前，20 mM钾离子中的钙离子/fmepp剂量/反应曲线向右移动。这些结果表明，锌离子通过电压门控钙离子通道进入神经末梢，这些通道与这些离子以复杂的方式相互作用，然后（a）在钙离子通常控制递质释放的位点作为部分激动剂起作用，（b）在神经末梢产生不可逆的变化，与fmepp的升高和随后的下降以及释放机制对钙离子和其他试剂的敏感性丧失有关。
