1. In skeletal muscle fibres, voltage-gated sodium channels are concen
trated at the neuromuscular junction. The effect of this accumulation
of sodium channels on action potential generation was investigated in
rat slow- and fast-twitch muscle fibres. 2. Intracellular microelectro
des were used to generate and record action potentials, from an impose
d membrane potential of -75 and -90 mV, in junctional and extrajunctio
nal regions of the muscle fibre. To identify junctional regions, prepa
rations were incubated with 5 x 10(-7) M d-tubocurarine (dTC) to block
muscle contraction in response to nerve stimulation whilst allowing e
ndplate potentials (EPPs) to be recorded. Injection of rectangular dep
olarizing current pulses initiated action potentials at the endplate w
ith threshold values several millivolts lower than those generated els
ewhere in the fibre. In addition, the maximum rate of rise of the acti
on potential was greater at the endplate than in extrajunctional regio
ns. 3. In other muscles, neuromuscular transmission was partially bloc
ked with dTC (2 x 10(-7) M), such that repetitive nerve stimulation ev
oked action potentials and EPPs in the same fibre. The threshold of th
ese nerve-evoked action potentials was approximately 50% lower than va
lues derived from action potentials generated by current injection. 4.
It is concluded that the threshold for action potential generation is
significantly lower at the neuromuscular junction than in extrajuncti
onal regions of skeletal muscle fibres. Furthermore, nerve-evoked curr
ent is more effective at generating an action potential than is inject
ed current.