Document Detail

Transmural heterogeneity of repolarization and Ca2+ handling in a model of mouse ventricular tissue.
MedLine Citation:
PMID:  20525874     Owner:  NLM     Status:  MEDLINE    
Mouse hearts have a diversity of action potentials (APs) generated by the cardiac myocytes from different regions. Recent evidence shows that cells from the epicardial and endocardial regions of the mouse ventricle have a diversity in Ca(2+) handling properties as well as K(+) current expression. To examine the mechanisms of AP generation, propagation, and stability in transmurally heterogeneous tissue, we developed a comprehensive model of the mouse cardiac cells from the epicardial and endocardial regions of the heart. Our computer model simulates the following differences between epicardial and endocardial myocytes: 1) AP duration is longer in endocardial and shorter in epicardial myocytes, 2) diastolic and systolic intracellular Ca(2+) concentration and intracellular Ca(2+) concentration transients are higher in paced endocardial and lower in epicardial myocytes, 3) Ca(2+) release rate is about two times larger in endocardial than in epicardial myocytes, and 4) Na(+)/Ca(2+) exchanger rate is greater in epicardial than in endocardial myocytes. Isolated epicardial cells showed a higher threshold for stability of AP generation but more complex patterns of AP duration at fast pacing rates. AP propagation velocities in the model of two-dimensional tissue are close to those measured experimentally. Simulations show that heterogeneity of repolarization and Ca(2+) handling are sustained across the mouse ventricular wall. Stability analysis of AP propagation in the two-dimensional model showed the generation of Ca(2+) alternans and more complex transmurally heterogeneous irregular structures of repolarization and intracellular Ca(2+) transients at fast pacing rates.
Vladimir E Bondarenko; Randall L Rasmusson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-06-04
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  299     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-30     Completed Date:  2010-08-30     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H454-69     Citation Subset:  IM    
Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, USA.
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MeSH Terms
Action Potentials
Calcium / metabolism*
Calcium Signaling*
Cardiac Pacing, Artificial
Computer Simulation
Endocardium / cytology,  metabolism*
Heart Ventricles / cytology,  metabolism*
Models, Cardiovascular
Myocytes, Cardiac / metabolism*
Pericardium / cytology,  metabolism*
Potassium / metabolism
Sodium-Calcium Exchanger / metabolism
Time Factors
Grant Support
Reg. No./Substance:
0/Sodium-Calcium Exchanger; 7440-09-7/Potassium; 7440-70-2/Calcium

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