Changes of quantal transmitter release caused by gadolinium ions at the frog neuromuscular junction

1 The actions of the trivalent cation, gadolinium (Gd3+), were studied on frog isolated neuromuscular preparations by conventional electrophysiological techniques. 2 Gd3+(450 μm) applied to normal or formamide‐treated cutaneous pectoris nerve‐muscle preparations induced, after a short delay, a complete block of neuromuscular transmission. The reversibility of the effect was dependent on the time of exposure. 3 Gd3+(5–450 μm) had no consistent effect on the resting membrane potential of the muscle fibres. 4 Gd3+(5–40 μm) applied to preparations equilibrated in solutions containing high Mg2+and low Ca2+reduced the mean quantal content of endplate potentials (e.p.ps) in a dose‐dependent manner. Under those conditions, 3,4‐diaminopyridine (10 μm) consistently reversed the depression of evoked quantal release. 5 The calcium current entering motor nerve terminals, revealed after blocking presynaptic potassium currents with tetraethylammonium (10 mm) in the presence of elevated extracellular Ca2+(8 mm), was markedly reduced by Gd3+(0.2–0.5 mm). 6 Gd3+(40–200 μm) increased the frequency of spontaneous miniature endplate potentials (m.e.p.ps) in junctions bathed either in normal Ringer solution or in a nominally Ca2+‐free medium supplemented with 0.7 μm tetrodotoxin. This effect may be due to Gd3+entry into the nerve endings since it is not reversed upon removal of extracellular Gd3+with chelators (1 mm EGTA or EDTA). Gd3+also enhanced the frequency of me.p.ps appearing after each nerve stimulus in junctions bathed in a medium containing high Mg2+and low Ca2+ 7 Gd3+, in concentrations higher than 100 μm, decreased reversibly the amplitude of m.e.p.ps suggesting a postsynaptic action. 8 It is concluded that the block of nerve‐impulse evoked quantal release caused by Gd3+is related to its ability to block the calcium current entering the nerve endings, supporting the view that Gd3+blocks N‐type Ca2+channels; while the enhancement of spontaneous quantal release is probably the result of Gd3+entry into motor nerve endings. Besides its dual prejunctional effects on quantal release it is suggested that Gd3+exerts a postsynaptic action on the endplate acetylcholine receptor‐channel complex.