On the mechanism by which calcium and magnesium affect the release of transmitter by nerve impulses.

1. The relationship between the quantal content of end-plate potentials (e.p.p.s) and the bathing [Ca] and [Mg] was determined at neuromuscular junctions in the rat diaphragm in vitro.2. E.p.p.s were recorded intracellularly from preparations exposed to solutions with [Ca] between 0.05 and 10 mM and [Mg] between 0.1 and 12.5 mM. The quantal content of e.p.p.s was increased by raising the [Ca] over this range and decreased by raising the [Mg]. There appeared to be competition of Mg with Ca at three sites in the nerve terminal membrane.3. A kinetic scheme based on competition of Ca and Mg at three sites could quantitatively explain the effects of Ca and Mg upon the quantal content of e.p.p.s and also the effects of these ions upon miniature end-plate potential frequency.