Use-Dependent Fade And 2-Rate Recovery Of A Naloxone-Sensitive Inhibition In The Cat Superior Cervical-Ganglion

In anaesthetized cats, a short train to the cervical sympathetic trunk (CST), of frequency between 0.5 and 5.0 Hz, inhibited the postganglionic compound action potential (CAP) evoked by a test shock to the CST. When the CST was split into two bundles, the inhibition was obtained both homosynaptically and heterosynaptically. The inhibition was antagonized by naloxone and enhanced by peptidase inhibitors. Leu-enkephalin (ENK), injected into the arterial supply of the superior cervical ganglion (SCG) depressed the CAP. The ENK-evoked inhibition was antagonized by naloxone, enhanced by peptidase inhibitors and was occluded by the train-evoked inhibition. After prolonged stimulation of the CST (5-20 min at 5 Hz), the inhibition produced by a short train was depressed (faded). The fade was greater the longer the stimulation. After 20 min of stimulation the inhibition was absent. At this time the depressant effect of ENK was unchanged. When only one bundle of the split CST was stimulated at 5 Hz for 20 min, only the inhibition produced by that bundle faded, although both bundles converged onto a common set of ganglion cells. Thus, the fade is not due to receptor desensitization but more likely to failure to release the inhibitory mediator by the overstimulated axons. When, after 20 min of 5 Hz stimulation, no further stimuli were applied, the inhibition recovered in 60 min (fast recovery). However, recovery was slower when stimulation lasted longer than 20 min. Recovery took three days when stimulation lasted 80 min (slow recovery). The inhibition was markedly depressed after application of colchicine to the CST three days earlier. This suggests significant spontaneous release of the endogenous opioid. This treatment also prevented the slow recovery from the fade. The fast recovery from the fade was not prevented by protein synthesis inhibitors nor by a colchicine block of the CST. The data are consistent with the hypothesis that the transmitter mediating the naloxone-sensitive inhibition in the SCG of the cat is present in the preganglionic axon terminals in a small, readily releasable, pool which is exhausted by 20 min stimulation at 5 Hz. A presumably local mechanism, which is exhausted by 80 min of stimulation at 5 Hz, is responsible for the fast recovery. The slow recovery presumably involves protein synthesis and axonal transport.