Zinc competitively inhibits calcium-dependent release of transmitter at the mouse neuromuscular junction

The effect of zinc on the release of transmitter was investigated in preparations of mouse diaphragm by conventional microelectrode techniques. The frequency (F) of miniature end-plate potentials (MEPPs), elevated by Ca2+ in high K+ medium, was reduced by zinc in a concentration-dependent fashion. When the extracellular concentration of Ca2+ ([Ca2+]o) was varied in the absence of zinc, a linear relationship between log(F) and log([Ca2+]o) was obtained. When the effect of zinc was depicted graphically, it was found that zinc shifted the relationship between log(F) and log([Ca2+]o) to the right, with respect to the control in the absence of zinc, without altering the slope. Zinc also reduced the quantal content (m) of end-plate potentials (EPPs). As [Ca2+]o was varied in the absence of zinc, a linear relationship between ln(m) and ln([Ca2+]o) was observed. Zinc shifted this linear relationship between ln(m) and ln([Ca2+]o) to the right, with respect to the control, without altering the slope. Thus, zinc reduced both the asynchronous and the phasic release of transmitter. These results suggest that zinc competes with Ca2+, and this conclusion is confirmed by examination of a modified Lineweaver-Burk plot of the data. Zinc probably inhibits the entry of Ca2+ into the nerve terminals, thereby inhibiting transmitter release.