Abstract/Details

Mechanisms Underlying Angiotensin II Type 1 Receptor Mediated Electrical Remodeling in Left Ventricular Myocytes


2011 2011

Other formats: Order a copy

Abstract (summary)

The angiotensin II type 1 (AT1) receptor is a G protein coupled receptor that is highly active in various cardiac disease states. Both the AT1 receptor and its primary effector, angiotensin II (A2), are known to be expressed in cardiac tissue. AT1 receptor activation leads to the transactivation of various intracellular signaling pathways that are known to be responsible for physiological and pathological changes in both cardiac structure and function. In particular, AT1 receptors are involved in physiological adaptation to increased hemodynamic load, but they are also involved in the development of pathological cardiac hypertrophy, which is characterized by structural and electrical remodeling during the progression into heart failure. However, the AT1 receptor-mediated mechanisms underlying these changes are unclear. Therefore, the overall aim of this study was to highlight the importance of AT1 receptors in mechanical stress-induced electrical remodeling and to understand the mechanisms underlying AT1 receptor-mediated regulation.

The following is a summary of our findings. Using the whole-cell patch clamp technique on isolated left ventricular myocytes from a pressure overload-induced mouse model of cardiac hypertrophy, we measured the time dependence of reductions in two predominant repolarizing currents, the fast and slow components of the transient outward K+-current (Ito,fast and IK,slow). These reductions preceded structural remodeling of the heart. We also present evidence supporting our hypothesis that AT1 receptors mediate these reductions. Moreover, we present evidence supporting a novel hypothesis that AT1 receptor-mediated downregulation of Ito,fast and IK,slow does not involve G protein stimulation; rather, it appears to depend on receptor internalization, which leads to reductions in functional Ito,fast and IK,slow channel densities. Finally, with the aid of a computational action potential model and multivariable linear regression, we quantified the relative significance of various electrophysiological parameters, including Ito,fast and IK,slow properties, on the determination of the action potential morphology.

The results presented in this work provide new insights into AT1 receptor-mediated changes that are typically associated with heart failure.

Indexing (details)


Subject
Biomedical engineering;
Physiology;
Biophysics
Classification
0541: Biomedical engineering
0719: Physiology
0786: Biophysics
Identifier / keyword
Applied sciences; Biological sciences; Angiotensin; Cardiac myocytes; Electrical remodeling; Electrophysiology; Hypertrophy
Title
Mechanisms Underlying Angiotensin II Type 1 Receptor Mediated Electrical Remodeling in Left Ventricular Myocytes
Author
Kim, Jeremy Hyonjoon
Number of pages
123
Publication year
2011
Degree date
2011
School code
0771
Source
DAI-B 72/12, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781124912769
Advisor
Mathias, Richard T.; Entcheva, Emilia
Committee member
Cohen, Ira S.; Lin, Richard Z.; Shirokov, Roman
University/institution
State University of New York at Stony Brook
Department
Biomedical Engineering
University location
United States -- New York
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3474561
ProQuest document ID
898891291
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/898891291
Access the complete full text

You can get the full text of this document if it is part of your institution's ProQuest subscription.

Try one of the following:

  • Connect to ProQuest through your library network and search for the document from there.
  • Request the document from your library.
  • Go to the ProQuest login page and enter a ProQuest or My Research username / password.