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• W2073201536 abstract "1 The subcellular mechanism and site of action of linopirdine or DuP 996 (3,3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one) was investigated at the frog neuromuscular junction, using miniature endplate potential (m.e.p.p.) counts and a new method for obtaining unbiased estimates of n (number of functional release sites), p (probability of release), and varsp (spatial variance in p). 2 DuP 996 produced an increase in m (no. of quanta released), which was due to an increase in n and p. The increase in m was concentration-dependent over a range of 0.1–100 μm and completely reversible with 15 min of wash. There was a saturation in the increase in p, but not in the increase in m and n, for [DuP 996] >10 μm. By contrast, there was no major change in varsp. 3 Block of presynaptic Na+- and Ca2+-channels with 3 μm tetrodotoxin and 1.8 mm Co2+prevented the m.e.p.p. frequency increase to DuP 996, and this effect was completely reversed by washing. 4 Application of the neuronal Ca2+-channel blocker, ω-conotoxin GVIA (1 μm) brought about a rapid and profound decrease in the m.e.p.p. frequency increase produced by DuP 996. The effect of the toxin was not reversed by prolonged washing. 5 Block of voltage-gated K+-channels with 100 μm 4-aminopyridine (4-AP) resulted in only a small (28%) increase in m. The combination of 4-AP (100 μm) and DuP 996 (10 μm) produced an increase in m (189%) which was much greater than the sum of the responses to each agent alone. This increase in m was due solely to an increase in n, as p and varsp were unchanged. 6 For [DuP 996] up to 100 μm, there was no apparent change in the mean size, amplitude distribution, or time course of m.e.p.ps, signifying that it had no anticholinesterase activity. 7 It is concluded that DuP 996 increases the release of quantal transmitter but not the postsynaptic response to the quanta. This appears to involve an effect at the nerve terminal membrane, most likely an increase in Ca2+-conductance, and not an action to block K+-conductance or to release Ca2+from intraterminal organelles." @default.
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• W2073201536 date "1994-04-01" @default.
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• W2073201536 title "Effect of the putative cognitive enhancer, linopirdine (DuP 996), on quantal parameters of acetylcholine release at the frog neuromuscular junction" @default.
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• W2073201536 doi "https://doi.org/10.1111/j.1476-5381.1994.tb14858.x" @default.
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