Molecular and functional remodeling of I(to) by angiotensin II in the mouse left ventricle
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Molecular and functional remodeling of I(to) by angiotensin II in the mouse left ventricle. / Tozakidou, Magdalini; Goltz, Diane; Hagenström, Till; Budack, Mareike K; Vitzthum, Helga; Szlachta, Kamila; Bähring, Robert; Ehmke, Heimo.
in: J MOL CELL CARDIOL, Jahrgang 48, Nr. 1, 01.2010, S. 140-51.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Molecular and functional remodeling of I(to) by angiotensin II in the mouse left ventricle
AU - Tozakidou, Magdalini
AU - Goltz, Diane
AU - Hagenström, Till
AU - Budack, Mareike K
AU - Vitzthum, Helga
AU - Szlachta, Kamila
AU - Bähring, Robert
AU - Ehmke, Heimo
N1 - Copyright 2009 Elsevier Inc. All rights reserved.
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - Angiotensin II
KW - Animals
KW - Blotting, Western
KW - Electrophysiology
KW - Heart Ventricles
KW - Hemodynamics
KW - Kv Channel-Interacting Proteins
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Potassium Channels
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Shal Potassium Channels
KW - Vasoconstrictor Agents
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.yjmcc.2009.08.027
DO - 10.1016/j.yjmcc.2009.08.027
M3 - SCORING: Journal article
C2 - 19744491
VL - 48
SP - 140
EP - 151
JO - J MOL CELL CARDIOL
JF - J MOL CELL CARDIOL
SN - 0022-2828
IS - 1
ER -
