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

Abstract

SUMMARY1. 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.2. 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 141 ms, and generally a larger amplitude. These were designated 'slow m.e.p.p.s'.3. 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

Tetrahydroaminoacridine (tacrine) stimulates neurosecretion at mammalian motor endplates

“…Colchicine (5mM) prevented tacrine from inducing slow m.e.p.ps as shown by the amplitude and time-to-peak histograms of Figure 3 therefore nerve impulses fail to release such quanta of ACh (Thesleff, 1986 (Dolly et al, 1987). In fact their frequency gradually increases with the time of paralysis (Kim et al, 1984). Figure 5 illustrates amplitude and time-to-peak distributions of m.e.p.ps in rat extensor digitorum longus muscles paralysed for 12-13 days by botulinum neurotoxin A.…”

“…Slow-rising, large-amplitude and calcium-insensitive m.e.p.ps are also present at endplates with regenerating motor nerve terminals (Bennett et al, 1973;Colmeus et al, 1982). They are particularly prominent in muscles chronically paralysed by botulinum toxin (Colmeus et al, 1982;Kim et al, 1984), tetrodotoxin (Gundersen, 1987) or curare (Ding et al, 1983). It has been suggested (Thesleff et al, 1989;) that the source for such potentials are the large, dense-cored synaptic vesicles which, in addition to ACh, contain various neuropeptides believed to have trophic actions on the muscle cell (see, Ochs, 1988).…”

“…As shown by Kim et al (1984), this type of toxin administration causes complete paralysis of the muscle and induces, within 7-10 days the appearance of giant or slow m.e.p.ps at a frequency of 0.1-1 Hz. The rats were killed by diethylether before removal of the muscle.…”

“…In experiments not involving nerve stimulation, tetrodotoxin (TTX) at a concentration of nerve stimulation. Synaptic potentials were analysed for frequency, amplitude and time-to-peak with an ABC 80 microcomputer with Data Disk 82 double floppy disk unit as described in detail by Colmeus et al (1982) and Kim et al (1984). The amplitude of the potentials was calculated for a resting membrane potential of -75mV and an ACh reversal potential of OmV (Katz & Thesleff, 1957 (Kim et al, 1984).…”

“…Synaptic potentials were analysed for frequency, amplitude and time-to-peak with an ABC 80 microcomputer with Data Disk 82 double floppy disk unit as described in detail by Colmeus et al (1982) and Kim et al (1984). The amplitude of the potentials was calculated for a resting membrane potential of -75mV and an ACh reversal potential of OmV (Katz & Thesleff, 1957 (Kim et al, 1984). Such slow m.e.p.ps constituted on the average 1.8 + 0.43% (mean + s.e.mean; number of observations is given in the legend of Figure 2) of all m.e.p.ps (n = 2847) in untreated muscles and occurred at a mean frequency of 0.03 + 0.01 Hz.…”