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The effects of vesamicol on trains of endplate currents and on focally recorded nerve terminal currents at mammalian neuromuscular junctions
Author(s) -
Pemberton Karen E.,
Prior Chris,
Marshall Ian G.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14220.x
Subject(s) - chemistry , tetrodotoxin , motor nerve , neuromuscular junction , stimulation , neuromuscular transmission , biophysics , anatomy , neuroscience , endocrinology , biology
1 The effects of vesamicol, an inhibitor of vesicular acetylcholine (ACh) storage, were studied on trains of endplate currents (e.p.cs) in the cut rat hemidiaphragm nerve‐muscle preparation and on trains of focally recorded nerve terminal current waveforms in the mouse triangularis sterni nerve‐muscle preparation. 2 In the rat, 0.1 and 1 μ m (−)‐vesamicol produced an enhancement of the rundown of e.p.c. amplitudes during trains of high frequency (50 Hz) nerve stimulation. However, 1 μ m (+)‐vesamicol had no effect on the rundown of e.p.c. amplitudes. 3 In the mouse, high concentrations of (−)‐vesamicol (10–100 μ m ) produced a concentration‐ and stimulation‐dependent decrease in the amplitude of the second negative‐going deflection of focally recorded nerve terminal current waveforms. 4 At 1 m m , (−)‐vesamicol produced a stimulation‐independent decrease in the amplitude of the first negative‐going deflection of the nerve terminal current waveforms, an increase in signal delay and evidence of nerve conduction failure. These all indicate a local anaesthetic‐like block of nodal Na + ‐channels. 5 In contrast to its effects on trains of e.p.cs, the effects of vesamicol on the nerve terminal current waveforms were not stereoselective, the (+)‐isomer being equipotent with the (−)‐isomer. 6 Low concentrations of the Na + ‐channel blocking toxin, tetrodotoxin (15–60 n m ), produced similar changes in the focally recorded nerve terminal current waveforms to those seen with vesamicol. 7 It is concluded that the stereoselective rundown of e.p.c. amplitudes produced by (−)‐vesamicol is due to an effect, either direct or indirect, on ACh mobilization within motor nerve terminals. Furthermore, in mammalian species, the inhibitory effects of vesamicol on nodal Na + ‐channels which are seen at high concentrations do not contribute to the principal neuromuscular effects of the compound.