Verapamil-induced transmitter release in rat diaphragm muscle

Verapamil was examined for its effect on the frequency of miniature end-plate potential (m.e.p.p.) in rat diaphragm muscles. Verapamil (5 x 10(-5) M) raised the m.e.p.p. frequency. This effect was reversible, reproducible, and concentration dependent. The rise in the frequency was maintained in the presence of external Ca++ but was transient in the absence of external Ca++. Lowering the temperature to 20 degrees C slightly decreased the average frequency of m.e.p.p. in the normal medium. The effect of verapamil was also present at a low temperature but was delayed in its onset. The resting membrane potential of the muscle fiber was not affected by the agent. These results suggest the possibility that verapamil increases the transmitter release from motor nerve terminals, and the effect is possibly due to a release of Ca++ for its initiation, but is dependent on external Ca++ for its maintenance.