UNIVERSITY OF BUCHAREST
FACULTY OF PHYSICS

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Conference: Bucharest University Faculty of Physics 2004 Meeting


Section: Electricity and Biophysics


Title:
Effect of tricyclic antidepressants on the frog epithelium pretreated with trypsin


Authors:
Prica C.†, Neaga E.†, Macri B.†, #, Flonta M.-L.†


Affiliation:
†Department of Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei, 91-95, Bucharest, R-050095, Romania

#Department of NeuroPsychoPharmacology, INSERM U288, Faculté de Medicine Pitie-Salpètriêre, 91, Bd de l’Hôpital, Paris Cedex 13, France


E-mail
prica_corina@hotmail.com


Keywords:
EnaC, trypsin, antidepressant


Abstract:
Our study was undertaken with the aim of testing the action of tricyclic antidepressants, imipramine (IMI) and desipramine (DES) on the epithelium sodium channel (ENaC) using the voltage-clamp technique on the frog epithelium (Rana ridibunda) as previously described for amitriptyline (Pena et al., 2002). The epithelium sodium channel belongs to Deg/ENaC family, like ASICs and many other putative members in the brain. It was studied the effect of imipramine and his metabolite desipramine on the short-circuit current (Isc) and transmembrane conductance (Gt) on the range of concentration of 1 ìM to 200 ìM. We observed a dose-dependent activation of the epithelial sodium channel, with a maximal effect at 100 microM tricyclic antidepressant. The application (time = 10 s up to several min) of 100 microM DES modified the time recovery. A previously treatment with 100 microg/ml trypsin on ventral part of the frog skin, induced a decrease of the Isc amplitude and slower reduction of the Gt amplitude. The mechanism of activation due to the tricyclic compound is different from the mechanism of activation caused by accumumation of the Na ions. The self-inhibition due to sodium disappears on the treatment with trypsin but does`t affects the activation due to tricyclic antidepressants. It was also tested the effect of 100 microM desipramine on artificial lipid bilayers containing phosphatidylcholine and phosphatidylcholine-cholesterol. The lipid bilayer capacitance increases and the effect on the membrane conductance is insignificant. The effect of tricyclic antidepressants on the ENaC is not due to a direct interaction of the drug with the lipid bilayer. The mechanism of regulation of the channel after activation with tricyclics is based on the feedback inhibition. Reference: Pena F, Neaga E, Amuzescu B, Nitu A, Flonta ML, Amitriptyline has a dual effect on the conductive properties of the epithelial Na channel, J Pharm Pharmacol. 2002 54(10):1393-8. Keywords: antidepressants, ENaC, trypsin