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Table of Contents
30, No. 4, 2012
Issue release date: September 2012
Section title: Original Paper
Cell Physiol Biochem 2012;30:863-875

Inhibitory Effect of Furosemide on Non-Selective Voltage-Independent Cation Channels in Human Erythrocytes

Kucherenko Y.V.a,b · Lang F.a
aDepartment of Physiology Institute I, Eberhard-Karls Universität Tübingen, bInstitute for Problems of Cryobiology and Cryomedicine of the Ukrainian National Academy of Sciences, Kharkov
email Corresponding Author

Florian Lang

Department of Physiology, University of Tübingen

Gmelinstr. 5, D-72076 Tübingen (Germany)

Tel. +49-70712972194, Fax +49-7071295618, E-Mail florian.lang@uni-tuebingen.de

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Background: Furosemide, a loop diuretic inhibiting the renal tubular Na+,K+,2Cl- cotransporter, has been shown to decrease cytosolic Ca2+ concentration ([Ca2+]i) in platelets and erythrocytes. [Ca2+]i in erythrocytes is a function of Ca2+ permeable cation channels. Activation of those channels e.g. by energy depletion or oxidative stress leads to increase of [Ca2+]i, which in turn triggers eryptosis, a suicidal erythrocyte death characterized by cell membrane scrambling. The present study was performed to explore whether furosemide influences the cation channels and thus influences eryptosis. Methods: Cation channel activity was determined by whole-cell patch clamp, [Ca2+]i utilizing Fluo3 fluorescence and annexin V binding to estimate cell membrane scrambling with phosphatidylserine exposure. Results: A 45 min exposure to furosemide (10 and 100 µM) slightly, but significantly decreased cation channel activity and [Ca2+]i in human erythrocytes drawn from healthy individuals. ATP-depletion (> 3 hours, +37°C, 6 mM ionosine and 6 mM iodoacetic acid) enhanced the non-selective cation channel activity, increased [Ca2+]i and triggered cell membrane scrambling, effects significantly blunted by furosemide (10 – 100 µM). Oxidative stress by exposure to tert-butylhydroperoxide (0.1 –1 mM) similarly enhanced the non-selective cation channels activity, increased [Ca2+]i and triggered cell membrane scrambling, effects again significantly blunted by furosemide (10 – 100 µM). Conclusions: The present study shows for the first time that the loop diuretic furosemide applied at micromolar concentrations (10 – 100 µM) inhibits non-selective cation channel activity in and eryptosis of human erythrocytes.

© 2012 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: July 27, 2012
Published online: August 20, 2012
Issue release date: September 2012

Number of Print Pages: 13
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

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