Spontaneous activity at long-term silenced synapses in rat muscle

1. The impulse activity in the sciatic nerve of rats was blocked for 30-59 days by a chronic infusion of tetrodotoxin (TTX) into a cuff around the nerve from an external mechanical pump. After this treatment the extensor digitorum longus muscle was isolated and the electrical activity at the endplates was recorded by intracellular electrodes. Endplates in the paralysed muscles were still functional as the muscle contracted briskly upon stimulation of the nerve distal to the block. 2. The spontaneous miniature endplate potentials (MEPPs) differed from those in normal muscles in having a more variable amplitude; 24% of the events were more than twice as large as the modal amplitude. In 30% of the fibres the largest of these 'giant' MEPPs (GMEPPs) triggered muscle action potentials. The amplitude distributions often had suggestive peaks indicating that the GMEPPs might consist of multiple quanta of the same size as those constituting the nerve impulse-evoked endplate potentials (EPPs). 3. The GMEPPs were more prolonged, but were similar in shape to MEPPs from normal muscles, with a smooth, relatively fast rising phase and a more prolonged decay. The mean time-to-peak was higher than for impulse-evoked EPPs of the same size, suggesting that the spontaneous release was more distant or less synchronized than after a nerve impulse. The half-decay time of the GMEPPs showed no large increase with increasing amplitude suggesting that the release of transmitter was not focal. The half-decay times were, however, longer than for impulse-evoked EPPs of the same size, suggesting that the spontaneous release might be less distributed than impulse-evoked release. 4. GMEPPs were not influenced by TTX, they were larger than the impulse-evoked EPPs in solutions containing high Mg2+ and low Ca2+, and they were not increased by high extracellular Ca2+ concentrations. Thus, the GMEPPs were not caused by spontaneous action potentials and probably not by Ca2+ influx. 5. In most cases the frequency of large and small MEPPs in paralysed muscles was influenced in the same way as those in normal muscles. It was increased by an increase in the extracellular K+ concentration or osmolarity, and reduced by a decrease in Ca2+ or an increase in Mg2+. The frequency was increased by Ruthenium Red. Also, like MEPPs in normal muscles, the frequency of small MEPPs in paralysed muscles was increased by increasing the extracellular Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)