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. 1994 Jul 1;478(Pt 1):125–136. doi: 10.1113/jphysiol.1994.sp020236

The upregulation of acetylcholine release at endplates of alpha-bungarotoxin-treated rats: its dependency on calcium.

J J Plomp 1, G T van Kempen 1, P C Molenaar 1
PMCID: PMC1155651  PMID: 7965828

Abstract

1. The presynaptic component of an adaptive feedback mechanism leading to increased acetylcholine (ACh) release was studied in endplates of diaphragms from rats treated chronically with alpha-bungarotoxin (alpha BTX). 2. Quantal contents were calculated 'directly' from the amplitude of miniature endplate potentials (MEPPs) and endplate potentials (EPPs) which were recorded after mu-conotoxin treatment to prevent muscle action potentials. 3. In vitro application of the Ca2+ channel blockers nifedipine (10 microM) or omega-conotoxin (40 nM) had no significant effect on the increased quantal content of endplates from alpha BTX-treated rats. 4. At control endplates, in vitro block of presynaptic K+ channels by 5 microM 3,4-diaminopyridine did increase the quantal content to a level which was similar to that found in endplates of alpha BTX-treated rats but also induced a broadening of EPPs, which was not found at endplates after alpha BTX treatment. 5. The difference between quantal contents of alpha BTX-treated and control rats was highly dependent on the [Ca2+]o/[Mg2+]o ratio when [Mg2+]o was fixed at 1 mM. At low [Ca2+]o, the quantal content of endplates from alpha BTX-treated rats was lower than that of controls while at [Ca2+]o in the normal and high range this was reversed. However, changing the [Ca2+]o/[Mg2+]o ratio by means of [Mg2+]o, at a fixed [Ca2+]o of 2 mM, did not influence the relative increase of quantal contents at endplates from alpha BTX-treated rats. Double logarithmic plots of the 'toxin-induced' myasthenia gravis (TIMG) and control quantal content versus [Ca2+]o had an approximately linear part between 0.2 and 1.5 mM [Ca2+]o. The slopes of the TIMG and control lines were 1.81 and 0.96, indicating that the ACh release in TIMG muscles was more sensitive to changes of [Ca2+]o than controls. 6. At normal [Ca2+]o and [Mg2+]o, the depression of EPP amplitude during stimulation of the phrenic nerve at 30-50 Hz was somewhat larger at endplates from alpha BTX-treated rats than at control endplates. At low [Ca2+]o, the potentiation of EPP amplitudes during a stimulus train was much larger at endplates from alpha BTX-treated rats than from controls. 7. The results do not support the idea that the increased release of ACh is caused via regulatory effects on the presynaptic Ca2+ or K+ channels. Instead, the anomalous dependency of ACh release on Ca2+ in muscles of alpha BTX-treated rats suggests that a cytoplasmic, Ca(2+)-dependent, component is involved in the adaptive change of transmitter release.

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Selected References

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