On the site of action of hemicholinium-3 at the rat phrenic nerve-diaphragm preparation with special reference to its multiple presynaptic actions

Abstract

Sites of action of hemicholinium-3 (HC-3) at the isolated rat phrenic nerve-diaphragm preparation were investigated through its effects on muscle twitch response, intracellular end-plate potential, acetylcholine (ACh) sensitivity of the end-plate, ACh release from the motor nerve, post-tetanic potentiation and antidromic activity. HC-3 in low concentration selectively abolished the generation of antidromic activity and post-tetanic potentiation without affecting the transmission, which was not reversed by an addition of choline, indicating a depressive effect of HC-3 on the cholinoceptive site at the motor nerve terminals. In addition, HC-3 in high concentration showed a curare-like postsynaptic action on muscle twitch responses caused by nerve stimulation and retrograde injection of ACh into the venous drainage. The anatagonism of muscle twitch response between HC-3 and choline and the inhibitory action of HC-3 on ACh release, namely on the choline carrier, were observed only after a relatively high frequency of nerve stimulation at its low concentration. These results suggest the presence of multiple sites of action of HC-3 at the neuromuscular junction and their possible significance has been discussed with special reference to its presynaptic actions.