Miniature end-plate potentials in rat skeletal muscle poisoned with botulinum toxin.

摘要

Spontaneous transmitter release, recorded as miniature end-plate potentials (m.e.p.p.s), was studied in rat extensor digitorum longus (e.d.l.) and soleus muscles partially or completely paralysed by botulinum toxin type A (BoTx). Normal unpoisoned muscles were examined for comparison. Analysis of m.e.p.p.s in both normal and BoTx-poisoned muscles confirmed the presence of two populations of potentials. One population, which comprised about 96% of the m.e.p.p.s recorded at non-poisoned end-plates, was characterized by a uniform time course and a mean time-to-peak of 0.5-0.7 ms. These potentials had a shape and time-to-peak similar to that of quantal end-plate potentials (e.p.p.s) evoked by nerve stimuli. These were designated 'fast m.e.p.p.s'. The other population of m.e.p.p.s was characterized by a slower, more variable rise-time, the time-to-peak exceeding 1.1 ms, and generally a larger amplitude. These were designated 'slow m.e.p.p.s'. In both partial and complete paralysis by BoTx the frequency of fast m.e.p.p.s was reduced by more than 90% and the reduction lasted several weeks. After 6-10 days of poisoning the frequency of slow m.e.p.p.s gradually increased. The highest frequency of slow m.e.p.p.s (0.4 Hz) was recorded in the partially paralysed soleus muscle, the frequency being about ten times that at unpoisoned end-plates. In both partially paralysed muscles slow m.e.p.p. frequency returned towards normal 28 days after poisoning. A significant correlation (r = 0.67) was observed between the quantal content of e.p.p.s and the frequency of fast m.e.p.p.s in partially paralysed e.d.l. muscles. No significant correlation was observed between quantal content of e.p.p.s and the frequency of slow m.e.p.p.s. To further study if muscle activity influenced the appearance of slow m.e.p.p.s, partially paralysed soleus muscles were directly stimulated in vivo during the first 11-13 days following BoTx poisoning, using a stimulation pattern which inhibits nerve terminal sprouting and the appearance of denervation changes. This procedure did not alter the frequency of slow m.e.p.p.s as compared to unstimulated poisoned controls. It is concluded that enhancement of slow m.e.p.p. frequency in muscles poisoned with BoTx is related to the blockade of evoked Ca2+-dependent quantal transmitter release. However, additional factors influence this type of spontaneous and Ca2+-insensitive release of acetylcholine since there is a great variability between fibres and a time lag between the disappearance of fast m.e.p.p.s and the activation of slow m.e.p.p. frequency.(ABSTRACT TRUNCATED AT 400 WORDS)