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UNIVERSITY OF BUCHAREST
FACULTY OF PHYSICS Guest
2024-11-22 1:37 |
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Conference: Bucharest University Faculty of Physics 2003 Meeting
Section: Electricity and Biophysics
Title:
Dual effect of amitriptyline on amiloride-blockable acid-sensing ion channels
Authors:
Beatrice Mihaela Macri*, Bogdan Amuzescu*, Neaga Emil*, Cristina Dinu**, Maria-Luiza Flonta*
Affiliation:
* Departement of Animal Physiology and Biophysics, Faculty of Biology, Splaiul Independentei, 91-95, University of Bucharest, Romania
** Departement Cell Cultures, Ion Cantacuzino Institute, Bucharest, Romania
E-mail
Keywords:
Abstract:
Different hypothesis sustain the implication of acid-sensing ion channels (ASICs) in nociception. ASICs are cation channels from degenerin/epithelial sodium channel family (DEG/ENaC), possessing two hydrophobic transmembrane domains as a hallmark of this family. Several types of ASIC have been identified: ASIC1a (ASIC or BNaC2), ASIC2a (MDEG1, BNC1 or BNAC1), ASIC3 (DRASIC), which are directly activated by protons and ASIC4, a subtype insensitive to protons when it is expressed alone. HEK293 (human embryonic kidney) cells represent a useful tool for the study of ASIC1a channels, since they expresses endogenously this type of ASIC. We have studied the effects of amiloride and amitriptyline on proton-induced transient currents in whole-cell and outside-out configuration, voltage-clamped at –70 and –80 mV, respectively. pH titration of peak transient amplitude yielded a pEC50 of 6.51, therefore we computed dose-effect curves for the two drugs at pH 6.3 and 5.3, at concentrations in the range 0.1 – 50 microM. Amiloride elicited a pH-independent inhibition, while amitriptyline exerted a biphasic response, activation at low concentrations (maximal at 5 microM) and inhibition at higher ones.
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