The Journal of Neurophysiology Vol. 86 No. 1 July 2001, pp. 183-189
Copyright ©2001 by the American Physiological Society
Effects of Bis(7)-Tacrine on Spontaneous Synaptic Activity and on
the Nicotinic ACh Receptor of Torpedo Electric Organ
Esteve
Ros,1
Jordi
Aleu,1
Inmaculada
Gomez De
Aranda,1
Carles
Cantí,2
Yuan-Ping
Pang,3
Jordi
Marsal,1 and
Carles
Solsona1
1Laboratori de Neurobiologia Cellular i
Molecular, Departament de Biologia Cellular i Anatomia
Patològica, Facultat de Medicina, Hospital de Bellvitge,
Universitat de Barcelona, E-08907 L'Hospitalet de Llobregat, Spain;
2Department of Pharmacology, University College
London, London WC1E 6BT, United Kingdom; and
3Mayo Clinic Cancer Center and Department of
Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic,
Rochester, Minnesota 55905
Ros, Esteve,
Jordi Aleu,
Inmaculada Gomez De
Aranda,
Carles Cantí,
Yuan-Ping Pang,
Jordi Marsal, and
Carles Solsona.
Effects of Bis(7)-Tacrine on Spontaneous Synaptic Activity and on
the Nicotinic ACh Receptor of Torpedo Electric Organ. J. Neurophysiol. 86: 183-189, 2001. 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
-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.
