Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation Research
Search: search_blue_button Advanced Search
Circulation Research. 2003
Published online before print January 23, 2003, doi: 10.1161/01.RES.0000057996.20414.C6
A more recent version of this article appeared on February 21, 2003
This Article
Right arrow Full Text (PDF)
Right arrow Correction (v93,pe48)
Right arrow All Versions of this Article:
92/3/261    most recent
01.RES.0000057996.20414.C6v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Silva, J.
Right arrow Articles by Rudy, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Silva, J.
Right arrow Articles by Rudy, Y.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CALCIUM COMPOUNDS
*CALCIUM, ELEMENTAL
*POTASSIUM
*SODIUM
Related Collections
Right arrow Pacemaker
Right arrow Ion channels/membrane transport
Right arrow Gene therapy

Submitted on October 22, 2002
Revised on January 15, 2003
Accepted on January 15, 2003

Mechanism of Pacemaking in IK1-Downregulated Myocytes

Jonathan Silva and Yoram Rudy *

From the Cardiac Bioelectricity Research and Training Center, Case Western Reserve University, Cleveland, Ohio.

* To whom correspondence should be addressed. E-mail: yxr{at}po.cwru.edu.

Biological pacemakers were recently created by genetic suppression of inward rectifier potassium current, IK1, in guinea pig ventricular cells. We simulated these cells by adjusting IK1 conductance in the Luo-Rudy model of the guinea pig ventricular myocyte. After 81% IK1 suppression, the simulated cell reached steady state with pacemaker period of 594 ms. Pacemaking current is carried by the Na+-Ca2+ exchanger, INaCa, which depends on the intracellular calcium concentration [Ca2+]i. This [Ca2+]i dependence suggests responsiveness (increase in rate) to {beta}-adrenergic stimulation ({beta}AS), as observed experimentally. Simulations of {beta}AS demonstrate such responsiveness, which depends on INaCa expression. However, a simultaneous {beta}AS-mediated increase in the slow delayed rectifier, IKs, limits {beta}AS sensitivity.
Key words: pacemaker • arrhythmias • ion channels • gene therapy




This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
L. C. McSpadden, R. D. Kirkton, and N. Bursac
Electrotonic loading of anisotropic cardiac monolayers by unexcitable cells depends on connexin type and expression level
Am J Physiol Cell Physiol, August 1, 2009; 297(2): C339 - C351.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
M. E. Mangoni and J. Nargeot
Genesis and Regulation of the Heart Automaticity
Physiol Rev, July 1, 2008; 88(3): 919 - 982.
[Abstract] [Full Text] [PDF]

Home page
 EuropaceHome page
S. Peters, E. Schulze-Bahr, S. P. Etheridge, and M. Tristani-Firouzi
Sudden cardiac death in Andersen-Tawil syndrome
Europace, March 1, 2007; 9(3): 162 - 166.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
G. Seemann, F. B. Sachse, D. L. Weiss, L. J. Ptacek, and M. Tristani-Firouzi
Modeling of IK1 mutations in human left ventricular myocytes and tissue
Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H549 - H559.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Y. Kurata, H. Matsuda, I. Hisatome, and T. Shibamoto
Effects of pacemaker currents on creation and modulation of human ventricular pacemaker: theoretical study with application to biological pacemaker engineering
Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H701 - H718.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
H.-F. Tse, T. Xue, C.-P. Lau, C.-W. Siu, K. Wang, Q.-Y. Zhang, G. F. Tomaselli, F. G. Akar, and R. A. Li
Bioartificial Sinus Node Constructed via In Vivo Gene Transfer of an Engineered Pacemaker HCN Channel Reduces the Dependence on Electronic Pacemaker in a Sick-Sinus Syndrome Model
Circulation, September 5, 2006; 114(10): 1000 - 1011.
[Abstract] [Full Text] [PDF]

Home page
 Phil Trans R Soc AHome page
A. P Benson, R. H Clayton, A. V Holden, S. Kharche, and W. C Tong
Endogenous driving and synchronization in cardiac and uterine virtual tissues: bifurcations and local coupling
Phil Trans R Soc A, May 15, 2006; 364(1842): 1313 - 1327.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
E. M. Azene, T. Xue, E. Marban, G. F. Tomaselli, and R. A. Li
Non-equilibrium behavior of HCN channels: Insights into the role of HCN channels in native and engineered pacemakers
Cardiovasc Res, August 1, 2005; 67(2): 263 - 273.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
T. Krogh-Madsen, P. Schaffer, A. D. Skriver, L. K. Taylor, B. Pelzmann, B. Koidl, and M. R. Guevara
An ionic model for rhythmic activity in small clusters of embryonic chick ventricular cells
Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H398 - H413.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
K. Zorn-Pauly, P. Schaffer, B. Pelzmann, P. Lang, H. Machler, B. Rigler, and B. Koidl
If in left human atrium: a potential contributor to atrial ectopy
Cardiovasc Res, November 1, 2004; 64(2): 250 - 259.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
M. R. Rosen, P. R. Brink, I. S. Cohen, and R. B. Robinson
Genes, stem cells and biological pacemakers
Cardiovasc Res, October 1, 2004; 64(1): 12 - 23.
[Abstract] [Full Text] [PDF]


Circulation Research Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2003 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.