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 neuromuscular junctions. In addition, it reduced voltage-gated sodium and potassium currents in a use-dependent fashion, but had only a small effect on the presynaptic Ca(2+) conductance. By contrast, it blocked FM 1-43 vesicular uptake but not its release, in both species. Postsynaptically, T-588 reduced acetylcholine currents at the mammalian junction in a voltage-independent manner, but had no effect on the crayfish glutamate junction. All of these effects were rapidly reversible and were observed at concentrations close to the compound's acute protective level. We propose that this set of mechanisms, which reduces high-frequency synaptic transmission, is an important contributory factor in the neuroprotective action of T-588.
Hirata
K
K
Department of Physiology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Nakagawa
M
M
Urbano
F J
FJ
Rosato-Siri
M D
MD
Moreira
J E
JE
Uchitel
O D
OD
Sugimori
M
M
Llinás
R
R
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003400:Astacoidea; D002118:Calcium / Q000378:metabolism; D004048:Diethylamines / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D013572:Synaptic Vesicles / Q000187:drug effects* / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*
D004048:Diethylamines; D018696:Neuroprotective Agents; D015221:Potassium Channels; D015222:Sodium Channels; D013876:Thiophenes; C082372:T 588; D018698:Glutamic Acid; D002118:Calcium