Premium
Reversal by cysteine of the cadmium‐induced block of skeletal neuromuscular transmission in vitro
Author(s) -
Braga M.F.M.,
Rowan E.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.tb14468.x
Subject(s) - neuromuscular transmission , acetylcholine , neuromuscular junction , chemistry , cysteine , blockade , extracellular , stimulation , carbachol , neuromuscular blockade , ed50 , endocrinology , acetylcholine receptor , 4 aminopyridine , cadmium , in vitro , medicine , biophysics , biochemistry , anesthesia , receptor , biology , potassium channel , neuroscience , enzyme , organic chemistry
1 Neuromuscular transmission in isolated nerve‐muscle preparations was blocked by exposure to Cd 2+ for less than 30 min or more than 2 h. The abilities of cysteine, Ca 2+ or 3,4‐diaminopyridine (3,4‐DAP) to reverse the blockade induced by Cd 2+ were studied. 2 On the mouse hemidiaphragm preparation, exposure to Cd 2+ (10 μ m ) for 10 to 20 min induced a blockade which was easily reversed by increasing the extracellular Ca 2+ concentration (5–10 m m ) or by 3,4‐DAP (100 μ m ). Exposure to Cd 2+ (3–10 μ m ) for over 2 h led to a blockade which was not reversed by Ca 2+ (5–15 m m ) or 3,4‐DAP (100 μ m ). Cysteine (1 m m ) was able to reverse completely the blockade induced by both brief and prolonged exposures to Cd 2+ . 3 In chick biventer cervicis preparations, Cd 2+ (100 μ m ) decreased the twitch height of indirectly stimulated preparations without affecting responses to exogenously applied acetylcholine, carbachol or KCl. Cysteine (1–3 m m ) had no appreciable effect on twitch responses to indirect stimulation or to exogenously applied agonists but fully reversed the blockade induced by Cd 2+ (100 μ m ). 4 In mouse triangularis sterni preparations, Cd 2+ (1–30 μ m ) depressed the evoked quantal release of acetylcholine. Concentrations of Cd 2+ which completely blocked endplate potentials (e.p.ps) were without significant effect on miniature endplate potential (m.e.p.p.) amplitude and frequency or time constant of decay. Cysteine (1–10 m m ) alone had no effect on e.p.ps or m.e.p.ps, but completely reversed the blockade induced by Cd 2+ . 5 Extracellular recording of perineural waveforms from triangularis sterni preparations revealed that Cd 2+ was able to block the long‐lasting positive component that is sensitive to Ca 2+ channel blockers and the delayed negative deflection that is related to the Ca 2+ ‐activated K + current ( I K,Ca ) seen in the presence of 3,4‐DAP. Cysteine by itself had no effect on any component of the perineural waveform, but promptly reversed the blockade induced by Cd 2+ . 6 In addition to the competitive blocking action of Cd 2+ at the prejunctional Ca 2+ channels, long exposure to Cd 2+ leads to a blockade that is not competitive. This probably involves binding of Cd 2+ at an extracellular thiol site on, or close to, voltage‐operated Ca 2+ channels.