Please use this identifier to cite or link to this item:
http://hdl.handle.net/10261/24675
Share/Export:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Title: | Spironolactone and its main metabolite, canrenoic acid, block human ether-a-go-go–related gene channels |
Authors: | Caballero, Ricardo; Moreno de Alborán, Ignacio; González, Teresa CSIC ORCID; Arias, Cristina CSIC; Valenzuela, Carmen CSIC ORCID CVN; Delpón, Eva; Tamargo, Juan | Keywords: | Ion channels Potassium channels Patch-clamp techniques Spironolactone |
Issue Date: | 18-Feb-2003 | Publisher: | American Heart Association | Citation: | Circulation 107(6): 889-895 (2003) | Abstract: | Background— It has been demonstrated that spironolactone (SP) decreases the QT dispersion in chronic heart failure. In this study, the effects of SP and its metabolite, canrenoic acid (CA), on human ether-a-go-go–related gene (HERG) currents were analyzed. Methods and Results— HERG currents elicited in stably transfected Chinese hamster ovary cells were measured with the whole-cell patch-clamp technique. SP decreased HERG currents in a concentration-dependent manner (IC50=23.0±1.5 µmol/L) and shifted the midpoint of the activation curve to more negative potentials (Vh=-13.1±3.4 versus -18.9±3.6 mV, P<0.05) without modifying the activation and deactivation kinetics. SP-induced block (1 µmol/L) appeared at the range of membrane potentials coinciding with that of channel activation, and thereafter, it remained constant, reaching 24.7±3.8% at +60 mV (n=6, P<0.05). CA (0.01 nmol/L to 500 µmol/L) blocked HERG channels in a voltage- and frequency-independent manner. CA at 1 nmol/L shifted the midpoint of the activation curve to -19.9±1.8 mV and accelerated the time course of channel activation ({tau}=1064±125 versus 820±93 ms, n=11, P<0.01). The envelope of the tail test demonstrated that at the very beginning of the pulses to +40 mV (25 ms), a certain amount of block was apparent (31.3±9.9%). CA did not modify the voltage-dependence of HERG channel inactivation (Vh=-60.8±5.6 versus -62.9±3.1 mV, n=6, P>0.05) or the kinetics of the reactivation process at any potential tested. CA and aldosterone also blocked the native IKr in guinea-pig ventricular myocytes. | Description: | 8 pages, 6 figures. | Publisher version (URL): | http://dx.doi.org/10.1161/01.CIR.0000048189.58449.F7 | URI: | http://hdl.handle.net/10261/24675 | DOI: | 10.1161/01.CIR.0000048189.58449.F7 | ISSN: | 0009-7322 |
Appears in Collections: | (IIBM) Artículos |
Show full item record
CORE Recommender
SCOPUSTM
Citations
67
checked on Apr 20, 2024
WEB OF SCIENCETM
Citations
56
checked on Feb 23, 2024
Page view(s)
493
checked on Apr 23, 2024
Download(s)
326
checked on Apr 23, 2024
Google ScholarTM
Check
Altmetric
Altmetric
WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.