Nicotinic receptors on the rat phrenic nerve: evidence for negative feedback

The effects of low concentrations (nanomolar) of d-tubocurarine (TC) on end-plate potential (EPP) and miniature end-plate potential (MEPP) amplitude, and quantal transmitter release were examined at the rat neuromuscular junction in an attempt to identify the functional role of nicotinic receptors on the nerve terminal. TC (50 and 75 nM) significantly depressed the MEPP amplitude but not the amplitude of the initial EPPs during a train-of-six stimulation at 50 Hz. The lack of depression in EPP amplitude by TC was due to an increase in quantal release. The nearly equipotent response of the pre- and post-synaptic effects of TC suggests that the autoreceptors on the nerve terminal are very similar to the nicotinic receptors on the end-plate. These results suggest that nicotinic autoreceptors are functional even with a single action potential. The results support the hypothesis that ACh released from the nerve terminal normally has a negative feedback effect by depressing transmitter release.