Effects of manganese ions on verapamil-induced increase of spontaneous transmitter release in motor nerve endings of rat diaphragm preparations.

Effect of verapamil on the spontaneous transmitter release in the presence and absence of external calcium and manganese ions was examined by monitoring the frequency of miniature end-plate potentials (MEPPs) in the rat diaphragms. Verapamil (25 to 50 microM) caused a sustained increase in the MEPP frequency in a normal Ringer solution and a transient increase in a calcium-free solution without change in the resting potential of end-plate. A readmission of calcium restored the sustained stimulatory effect of verapamil. The stimulatory effect of verapamil in calcium-free solution and the restoration of the effect by the calcium readmission were both blocked by pretreatment with manganese ions. It is suggested that verapamil increases the spontaneous transmitter release from the motor nerve terminal by increasing axoplasmic calcium levels through release from intracellular stores. Calcium may be continuously supplied to these stores from the extracellular space in the presence of verapamil through a pathway that is inhibited by manganese.