Reduced facilitation and vesicular uptake in crustacean and mammalian neuromuscular junction by T-588, a neuroprotective compound

Bath application of compound T-588, a neuroprotective agent, reduced paired -pulse and repetitive-pulse facilitation at mammalian and crustacean neurom uscular junctions. In addition, it reduced voltage-gated sodium end potassi um currents in a use-dependent fashion, but had only a small effect on the presynaptic Ca2+ conductance. By contrast, it blocked FM 1-43 vesicular upt ake but not its release, in both species. Postsynaptically, T-588 reduced a cetylcholine currents at the mammalian junction in a voltage-independent ma nner, but had no effect on the crayfish glutamate junction. All of these ef fects were rapidly reversible and were observed at concentrations close to the compound's acute protective level. We propose that this set of mechanis ms, which reduces high-frequency synaptic transmission, is an important con tributory factor in the neuroprotective action of T-588.