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Molecular and functional remodeling of I(to) by angiotensin II in the mouse left ventricle.
J Mol Cell Cardiol. 2010 Jan; 48(1):140-51.JM

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.

Authors+Show Affiliations

Zentrum für Experimentelle Medizin, Institut für Vegetative Physiologie und Pathophysiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19744491

Citation

Tozakidou, Magdalini, et al. "Molecular and Functional Remodeling of I(to) By Angiotensin II in the Mouse Left Ventricle." Journal of Molecular and Cellular Cardiology, vol. 48, no. 1, 2010, pp. 140-51.
Tozakidou M, Goltz D, Hagenström T, et al. Molecular and functional remodeling of I(to) by angiotensin II in the mouse left ventricle. J Mol Cell Cardiol. 2010;48(1):140-51.
Tozakidou, M., Goltz, D., Hagenström, T., Budack, M. K., Vitzthum, H., Szlachta, K., Bähring, R., & Ehmke, H. (2010). Molecular and functional remodeling of I(to) by angiotensin II in the mouse left ventricle. Journal of Molecular and Cellular Cardiology, 48(1), 140-51. https://doi.org/10.1016/j.yjmcc.2009.08.027
Tozakidou M, et al. Molecular and Functional Remodeling of I(to) By Angiotensin II in the Mouse Left Ventricle. J Mol Cell Cardiol. 2010;48(1):140-51. PubMed PMID: 19744491.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2009/09/08/ PY - 2009/03/11/received PY - 2009/08/20/revised PY - 2009/08/27/accepted PY - 2009/9/12/entrez PY - 2009/9/12/pubmed PY - 2010/4/22/medline SP - 140 EP - 51 JF - Journal of molecular and cellular cardiology JO - J Mol Cell Cardiol VL - 48 IS - 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. SN - 1095-8584 UR - https://www.unboundmedicine.com/medline/citation/19744491/Molecular_and_functional_remodeling_of_I_to__by_angiotensin_II_in_the_mouse_left_ventricle_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2828(09)00370-8 DB - PRIME DP - Unbound Medicine ER -