Ahstr0rc.r: 2,3-Butanedione monoxime. also known as diacetyl monoxime, is a nucleophilic agent which dephosphorylates iicetylcholinesterase poisoned with organophosphates. This "chemical phosphatase" activity stimulated studies of the effect of 2.3-butanedione monoxime on phosphorylation-dependent cellular processes. As a result of these studies, we know that the drug affects a number of mechanisms including muscle contraction, ionic current flow and synaptic transmission. Furthermore. it may he used as a component of cardioplegic solutions since it protects cardiac tissue exposed to certain ischaemic conditions. While this MiniRewiev reveals the diversity of its cellular actions. there continues LO be unresolved questions regarding its molecular mechanism.

SUMMARY1. Extensor digitorum longus muscles of rats were paralysed with local, non-lethal doses of botulinum toxin Type A (BoTx). At 2 and 7 days after toxin injection, the nerve-muscle preparations were excised and end-plate currents analysed at 23 'C by dual-micro-electrode voltage clamp.2. At 2 days after BoTx injection, the growth time of miniature end-plate currents (m.e.p.c.s) increased from a rather narrow range with a mean of 0-59 to a mean of 1-35 ms with a large variability between m.e.p.c.s. End-plate currents (e.p.c.s) were reduced compared to unpoisoned muscle.

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Blockade of neuromuscular transmission was produced in the lower hind limb of the rat by local injection of either crystalline type A botulinum toxin or purified type B botulinum neurotoxin. At 1, 3, 5 and 7 days after injection, the extensor digitorum longus nerve-muscle preparation was excised and analyzed in vitro for alterations in spontaneous and nerve stimulus-evoked quantal transmitter release. Muscles receiving type A toxin were paralyzed up to and including 7 days after injection. Muscles treated with type B toxin, although completely paralyzed at 1 and 3 days, twitched in response to nerve stimulation at 5 and 7 days after injection. Both toxins induced a marked decrease in the frequency of miniature endplate potentials but type A did so to a greater extent. The remaining population of miniature endplate potentials contained a greater frequency of potentials with small or large amplitudes and prolonged rise times compared to normal muscle. These changes were more pronounced with type A toxin than with type B toxin. In the presence of alpha-dinitrophenol (1 mM), high frequency, fast-rising miniature endplate potentials of uniform size reappeared. High K+ (20 mM) was less effective in this respect. At 3 days after toxin injection nerve impulse evoked transmitter release was reduced more for type A treated muscles than for type B. However, 3,4-diaminopyridine, an agent which increases nerve-evoked transmitter release by increasing Ca2+ influx, was more effective in reversing the paralysis in type A than in type B-treated muscles.(ABSTRACT TRUNCATED AT 250 WORDS)