Effects of tubocurarine on end-plate current rundown and quantal content during rapid nerve stimulation in the snake.

1. The effects of tubocurarine, pancuronium, vecuronium and trimethyl-tubocurarine were examined on the amplitudes of end-plate currents (EPC) produced by repetitive nerve stimulation in cut voltage-clamped fibres of the costocutaneous muscle of the garter snake. The effects of tubocurarine were further studied on the amplitudes of miniature end-plate currents (MEPC) recorded immediately before the trains of nerve stimulation, thus allowing estimates to be made of EPC quantal content. 2. All four compounds increased the decline of EPC amplitude with successive impulses (rundown), compared with that observed in control end-plates. There was little effect on the decay time constants of EPC and the effects on rundown were not dependent on membrane potential, indicating that end-plate ion channel blockade was not a major effect in producing rundown. 3. In the presence of tubocurarine the quantal content of the EPC in the plateau phase of the trains was reduced when compared with control, indicating a reduction of transmitter mobilization. However tubocurarine had no significant effect on the quantal content of the first EPC of the trains, indicating that the decreased mobilization is not due to an initial effect on transmitter release. 4. It is suggested that the prejunctional effect of tubocurarine which results in increased EPC train rundown is primarily on transmitter mobilization. It is also suggested that the actions of tubocurarine and the other neuromuscular blockers tested are mediated through a prejunctional nicotinic receptor which may act as a positive feedback mechanism modulating transmitter mobilization.