AJP - Heart Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 292: H2854-H2866, 2007. First published February 2, 2007; doi:10.1152/ajpheart.01347.2006
0363-6135/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/6/H2854    most recent
01347.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (10)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Livshitz, L. M.
Right arrow Articles by Rudy, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Livshitz, L. M.
Right arrow Articles by Rudy, Y.

Regulation of Ca2+ and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents

Leonid M. Livshitz and Yoram Rudy

Cardiac Bioelectricity and Arrhythmia Center, Washington University in St. Louis, St. Louis, Missouri

Submitted 10 December 2006 ; accepted in final form 26 January 2007

Alternans of cardiac repolarization is associated with arrhythmias and sudden death. At the cellular level, alternans involves beat-to-beat oscillation of the action potential (AP) and possibly Ca2+ transient (CaT). Because of experimental difficulty in independently controlling the Ca2+ and electrical subsystems, mathematical modeling provides additional insights into mechanisms and causality. Pacing protocols were conducted in a canine ventricular myocyte model with the following results: 1) CaT alternans results from refractoriness of the sarcoplasmic reticulum Ca2+ release system; alternation of the L-type calcium current has a negligible effect; 2) CaT-AP coupling during late AP occurs through the sodium-calcium exchanger and underlies AP duration (APD) alternans; 3) increased Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity extends the range of CaT and APD alternans to slower frequencies and increases alternans magnitude; its decrease suppresses CaT and APD alternans, exerting an antiarrhythmic effect; and 4) increase of the rapid delayed rectifier current (IKr) also suppresses APD alternans but without suppressing CaT alternans. Thus CaMKII inhibition eliminates APD alternans by eliminating its cause (CaT alternans) while IKr enhancement does so by weakening CaT-APD coupling. The simulations identify combined CaMKII inhibition and IKr enhancement as a possible antiarrhythmic intervention.

arrhythmia; calcium; sudden death; electrophysiology; calcium/calmodulin-dependent protein kinase II


Address for reprint requests and other correspondence: Y. Rudy, Campus Box 1097 Whitaker Hall, Rm 290 Washington Univ. in St. Louis One Brookings Drive St. Louis, MO 63130–4899 (e-mail: rudy{at}wustl.edu)




This article has been cited by other articles:


Home page
 Phil Trans R Soc AHome page
J. T. Koivumaki, J. Takalo, T. Korhonen, P. Tavi, and M. Weckstrom
Modelling sarcoplasmic reticulum calcium ATPase and its regulation in cardiac myocytes
Phil Trans R Soc A, June 13, 2009; 367(1896): 2181 - 2202.
[Abstract] [Full Text] [PDF]

Home page
 Phil Trans R Soc AHome page
D. P. Nickerson and M. L. Buist
A physiome standards-based model publication paradigm
Phil Trans R Soc A, May 28, 2009; 367(1895): 1823 - 1844.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
K. F. Decker, J. Heijman, J. R. Silva, T. J. Hund, and Y. Rudy
Properties and ionic mechanisms of action potential adaptation, restitution, and accommodation in canine epicardium
Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H1017 - H1026.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
S. M. Narayan, J. D. Bayer, G. Lalani, and N. A. Trayanova
Action Potential Dynamics Explain Arrhythmic Vulnerability in Human Heart Failure A Clinical and Modeling Study Implicating Abnormal Calcium Handling.
J. Am. Coll. Cardiol., November 25, 2008; 52(22): 1782 - 1792.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
Y. Rudy, M. J. Ackerman, D. M. Bers, C. E. Clancy, S. R. Houser, B. London, A. D. McCulloch, D. A. Przywara, R. L. Rasmusson, R. J. Solaro, et al.
Systems Approach to Understanding Electromechanical Activity in the Human Heart: A National Heart, Lung, and Blood Institute Workshop Summary
Circulation, September 9, 2008; 118(11): 1202 - 1211.
[Abstract] [Full Text] [PDF]

Home page
 Brief BioinformHome page
P. J. Hunter, E. J. Crampin, and P. M. F. Nielsen
Bioinformatics, multiscale modeling and the IUPS Physiome Project
Brief Bioinform, July 1, 2008; 9(4): 333 - 343.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
D. Guo, L. Young, C. Patel, Z. Jiao, Y. Wu, T. Liu, P. R. Kowey, and G.-X. Yan
Calcium-activated chloride current contributes to action potential alternations in left ventricular hypertrophy rabbit
Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H97 - H104.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.