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Molecular and functional remodeling of I(to) by angiotensin II in the mouse left ventricle.
- Source :
-
Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2010 Jan; Vol. 48 (1), pp. 140-51. Date of Electronic Publication: 2009 Sep 08. - Publication Year :
- 2010
-
Abstract
- The transient outward potassium current (I(to)) in cardiac myocytes is mainly mediated by members of the Kv4 subfamily of voltage-gated potassium channels. Several in vitro studies have shown that angiotensin II (Ang II), which plays an important role in the development of cardiac hypertrophy, rapidly downregulates Kv4.3 mRNA expression. However, it is not clear whether Ang II regulates I(to)in vivo and whether this regulation may depend on alterations in Kv4.3 gene expression. To address this question, we determined the effects of acute (24 h) and chronic (14 days) exogenous infusions of Ang II on I(to) and the expression of its channel subunits in the mouse left ventricle. Ang II rapidly increased blood pressure and reduced Kv4.2 but not Kv4.3 mRNA levels in the absence of cardiac hypertrophy. In response to chronically elevated Ang II levels cardiac hypertrophy developed, which was associated with a downregulation of Kv4.2 and Kv4.3 mRNA levels, and an upregulation of Kv1.4 mRNA levels. In contrast, neither KChIP2 mRNA levels nor amplitude or macroscopic inactivation kinetics of I(to) were affected by the acute or chronic Ang II treatments. Consistent with the unchanged I(to) amplitude, Kv4.2, Kv4.3, and KChIP protein expression levels were similar after chronic Ang II and sham treatment. Our findings demonstrate that elevations of Ang II concentrations that induce hypertension and cardiac hypertrophy do not alter the amplitude of I(to) in the mouse left ventricle. Furthermore, they suggest that functional expression of cardiac I(to) in mice is stabilized by KChIP2.<br /> (Copyright 2009 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Blotting, Western
Electrophysiology
Hemodynamics drug effects
Kv Channel-Interacting Proteins metabolism
Male
Mice
Mice, Inbred C57BL
Potassium Channels metabolism
Reverse Transcriptase Polymerase Chain Reaction
Shal Potassium Channels metabolism
Angiotensin II pharmacology
Heart Ventricles drug effects
Heart Ventricles metabolism
Vasoconstrictor Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-8584
- Volume :
- 48
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of molecular and cellular cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 19744491
- Full Text :
- https://doi.org/10.1016/j.yjmcc.2009.08.027