The effect of (+)-tubocurarine on neuromuscular transmission during repetitive stimulation in the rat, mouse, and frog.

1. The effect of tubocurarine on amplitudes of end-plate currents in response to trains of repetitive stimulation (50-150/sec) was investigated in voltage-clamped muscle fibres of the rat, mouse and frog. 2. In rat and mouse muscle, the presence of tubocurarine led to a more rapid decline (rundown) in the amplitudes of successive end-plate currents during trains of impulses. In frog, tubocurarine caused an increase in apparent facilitation of end-plate current amplitudes during the first few impulses of repetitive stimulation; this increase was followed by a more rapid rundown of end-plate current amplitude. 3. These effects of tubocurarine appear not to be an artifact resulting from inadequate control of membrane potential in voltage-clamped fibres. 4. The more rapid rundown during trains of end-plate currents in the presence of tubocurarine showed little variation with membrane potential indicating that voltage-sensitive channel blockade by tubocurarine was not a major factor contributing to the rundown. 5. The effect of tubocurarine on the apparent facilitation and rundown of end-plate current amplitudes was typically decreased by reducing the frequency of stimulation. 6. These results suggest that tubocurarine affects transmitter release at neuromuscular junctions during repetitive stimulation.