Effects of bis(7)-tacrine on spontaneous synaptic activity and on the nicotinic ACh receptor of Torpedo electric organ

Esteve Ros, Jordi Aleu, Inmaculada Gomez De Aranda, Carles Cantí, Yuan-Ping Pang, Jordi Marsal, Carles Solsona

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Bis(7)-tacrine is a potent acetylcholinesterase inhibitor in which two tacrine molecules are linked by a heptylene chain. We tested the effects of bis(7)-tacrine on the spontaneous synaptic activity. Miniature endplate potentials (MEPPs) were recorded extracellularly on slices of electric organ of Torpedo marmorata. Bis(7)-tacrine, at a concentration of 100 nM, increased the magnitudes that describe MEPPs: amplitude, area, rise time, rate of rise, and half-width. We also tested the effect of bis(7)-tacrine on nicotinic acetylcholine receptors by analyzing the currents elicited by acetylcholine (100 μM) in Torpedo electric organ membranes transplanted in Xenopus laevis oocytes. Bis(7)-tacrine inhibited the acetylcholine-induced currents in a reversible manner (IC50 = 162 nM). The inhibition of nicotinic acetylcholine receptors was not voltage dependent, and bis(7)-tacrine increased the desensitization of nicotinic acetylcholine receptors. The Hill coefficient for bis(7)-tacrine was -0.72 ± 0.02, indicating that bis(7)-tacrine binds to the nicotinic acetylcholine receptor in a molecular ratio of 1:1, but does not affect the binding of α-bungarotoxin with the nicotinic acetylcholine receptor. In conclusion, bis(7)-tacrine greatly increases the spontaneous quantal release from peripheral cholinergic terminals at a much lower concentration than tacrine. Bis(7)-tacrine also blocks acetylcholine-induced currents of Torpedo electric organ, although the mechanism is different from that of tacrine: bis(7)-tacrine enhances desensitization, whereas tacrine reduces it.

Original languageEnglish (US)
Pages (from-to)183-189
Number of pages7
JournalJournal of Neurophysiology
Volume86
Issue number1
StatePublished - 2001

Fingerprint

Electric Organ
Torpedo
Nicotinic Receptors
Cholinergic Receptors
Tacrine
Acetylcholine
1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine
Bungarotoxins
Cholinesterase Inhibitors
Xenopus laevis
Cholinergic Agents
Inhibitory Concentration 50
Oocytes

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Ros, E., Aleu, J., Gomez De Aranda, I., Cantí, C., Pang, Y-P., Marsal, J., & Solsona, C. (2001). Effects of bis(7)-tacrine on spontaneous synaptic activity and on the nicotinic ACh receptor of Torpedo electric organ. Journal of Neurophysiology, 86(1), 183-189.

Effects of bis(7)-tacrine on spontaneous synaptic activity and on the nicotinic ACh receptor of Torpedo electric organ. / Ros, Esteve; Aleu, Jordi; Gomez De Aranda, Inmaculada; Cantí, Carles; Pang, Yuan-Ping; Marsal, Jordi; Solsona, Carles.

In: Journal of Neurophysiology, Vol. 86, No. 1, 2001, p. 183-189.

Research output: Contribution to journalArticle

Ros, E, Aleu, J, Gomez De Aranda, I, Cantí, C, Pang, Y-P, Marsal, J & Solsona, C 2001, 'Effects of bis(7)-tacrine on spontaneous synaptic activity and on the nicotinic ACh receptor of Torpedo electric organ', Journal of Neurophysiology, vol. 86, no. 1, pp. 183-189.
Ros, Esteve ; Aleu, Jordi ; Gomez De Aranda, Inmaculada ; Cantí, Carles ; Pang, Yuan-Ping ; Marsal, Jordi ; Solsona, Carles. / Effects of bis(7)-tacrine on spontaneous synaptic activity and on the nicotinic ACh receptor of Torpedo electric organ. In: Journal of Neurophysiology. 2001 ; Vol. 86, No. 1. pp. 183-189.
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