Mn and Mg influxes through Ca channels of motor nerve terminals are prevented by verapamil in frogs

At frog neuromuscular junctions immersed in solutions containing 0.5 mM Mn²⁺, verapamil (40 μM) reduced the increase in miniature end-plate potential (MEPP) frequency produced by tetanic stimulation (50 Hz, 2 min) of the motor nerve to 5% of that in the absence of verapamil. In solutions containing 5 mM Mg²⁺, verapamil reduced the tetanic increase in MEPP frequency to 8% of that in the absence of verapamil. Verapamil added to solutions containing 0.15 mM Ca²⁺ decreased the tetanic rise in MEPP frequency to 6% of the control value. In low Ca²⁺ (nominally Ca²⁺-free) solutions, verapamil decreased the tetanic rise to 70% of the control value. The present results suggest that Mn²⁺ and Mg²⁺, as well as Ca²⁺, enter the nerve terminal through Ca²⁺ channels during nerve stimulation and promote transmitter release. In addition to its effect on the Ca²⁺ channel, verapamil at higher concentrations appears to have inhibitory effects on the acetylcholine-gated end-plate channel and on the Na⁺ channel as suggested by its depressive effects on the amplitudes of MEPPs, end-plate potentials and nerve terminal action potentials.