The effects of imidazole on neuromuscular transmission and on synaptosomal calcium uptake in the rat.

The action of imidazole on neuromuscular transmission has been studied on the rat phrenic nerve-diaphragm preparation, and on the uptake of 45Ca on pinched-off presynaptic nerve terminals (synaptosomes) from rat brain. Imidazole (0.5--5 mM) reversibly increased the quantum content of evoked end-plate potentials and the mean amplitude of miniature end-plate potentials in preparations in which transmission was partially blocked with high Mg2+ and/or low Ca2+ concentrations. In solutions with a low Ca2+ concentration imidazole caused a smaller effect on the mean quantal content of evoked end-plate potentials. Imidazole also reversibly increased the amplitude of end-plate potentials in which transmission was blocked with tubocurarine. Imidazole decreased the frequency of miniature end-plate potentials in unstimulated preparations. Imidazole was devoid of effect on the compound action potential of the frog-sciatic nerve. Synaptosomes have been used to test the action of imidazole on 45Ca uptake. The substance (0.5--4 mM) enhanced the potassium stimulated uptake of 45Ca but had little or no effect on unstimulated synaptosomes. It is concluded that the excitatory effect of imidazole on the evoked release of the transmitter can be interpreted in terms of the increased calcium influx which it produced. The depressing effect on the frequency of miniature end-plate potentials is discussed in relation to the mechanisms that regulate the level of intracellular calcium.