Skip Navigation


Human Molecular Genetics Advance Access originally published online on June 16, 2006
Human Molecular Genetics 2006 15(15):2285-2297; doi:10.1093/hmg/ddl154
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
15/15/2285    most recent
ddl154v1
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 ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (17)
Google Scholar
Right arrow Articles by Kane, G. C.
Right arrow Articles by Terzic, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kane, G. C.
Right arrow Articles by Terzic, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

KCNJ11 gene knockout of the Kir6.2 KATP channel causes maladaptive remodeling and heart failure in hypertension

Garvan C. Kane1,2, Atta Behfar1,2, Roy B. Dyer1,2, D. Fearghas O'Cochlain1,2, Xiao-Ke Liu1,2, Denice M. Hodgson1,2, Santiago Reyes1,2, Takashi Miki3, Susumu Seino3 and Andre Terzic1,2,*

1 Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Department of Medicine, 2 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA and 3 Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

* To whom correspondence should be addressed at:, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel: +1 5072847517; Fax: +1 5072849111; Email: terzic.andre{at}mayo.edu

Received April 11, 2006; Accepted June 13, 2006

Heart failure is a growing epidemic, with systemic hypertension a major risk factor for development of disease. However, the molecular determinants that prevent the transition from a state of hypertensive load to that of overt cardiac failure remain largely unknown. Here in experimental hypertension, knockout of the KCNJ11 gene, encoding the Kir6.2 pore-forming subunit of the sarcolemmal ATP-sensitive potassium (KATP) channel, predisposed to heart failure and death. Defective decoding of hypertension-induced metabolic distress signals in the KATP channel knockout set in motion pathological calcium overload and aggravated cardiac remodeling through a calcium/calcineurin-dependent cyclosporine-sensitive pathway. Rescue of the failing KATP knockout phenotype was achieved by alternative control of myocardial calcium influx, bypassing uncoupled metabolic-electrical integration. The intact KCNJ11-encoded KATP channel is thus a required safety element preventing hypertension-induced heart failure, with channel dysfunction a molecular substrate for stress-associated channelopathy in cardiovascular disease.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. Marinovic, M. Ljubkovic, A. Stadnicka, Z. J. Bosnjak, and M. Bienengraeber
Role of sarcolemmal ATP-sensitive potassium channel in oxidative stress-induced apoptosis: mitochondrial connection
Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1317 - H1325.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. A. Burke, R. K. Mutharasan, and H. Ardehali
The Sulfonylurea Receptor, an Atypical ATP-Binding Cassette Protein, and Its Regulation of the KATP Channel
Circ. Res., February 1, 2008; 102(2): 164 - 176.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
Y. Yi, L. Dongmei, D. A. Phares, E. P. Weiss, J. Brandauer, and J. M. Hagberg
Association between KCNJ11 E23K genotype and cardiovascular and glucose metabolism phenotypes in older men and women
Exp Physiol, January 1, 2008; 93(1): 95 - 103.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
A. Jahangir, S. Sagar, and A. Terzic
Aging and cardioprotection
J Appl Physiol, December 1, 2007; 103(6): 2120 - 2128.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
S. E. Lehnart, M. J. Ackerman, D. W. Benson Jr, R. Brugada, C. E. Clancy, J. K. Donahue, A. L. George Jr, A. O. Grant, S. C. Groft, C. T. January, et al.
Inherited Arrhythmias: A National Heart, Lung, and Blood Institute and Office of Rare Diseases Workshop Consensus Report About the Diagnosis, Phenotyping, Molecular Mechanisms, and Therapeutic Approaches for Primary Cardiomyopathies of Gene Mutations Affecting Ion Channel Function
Circulation, November 13, 2007; 116(20): 2325 - 2345.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
D. A. Brown and R. L. Moore
Perspectives in innate and acquired cardioprotection: cardioprotection acquired through exercise
J Appl Physiol, November 1, 2007; 103(5): 1894 - 1899.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
L. V. Zingman, A. E. Alekseev, D. M. Hodgson-Zingman, and A. Terzic
ATP-sensitive potassium channels: metabolic sensing and cardioprotection
J Appl Physiol, November 1, 2007; 103(5): 1888 - 1893.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
R. J. Gumina, D. F. O'Cochlain, C. E. Kurtz, P. Bast, D. Pucar, P. Mishra, T. Miki, S. Seino, S. Macura, and A. Terzic
KATP channel knockout worsens myocardial calcium stress load in vivo and impairs recovery in stunned heart
Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1706 - H1713.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
A. Behfar, C. Perez-Terzic, R. S. Faustino, D. K. Arrell, D. M. Hodgson, S. Yamada, M. Puceat, N. Niederlander, A. E Alekseev, L. V. Zingman, et al.
Cardiopoietic programming of embryonic stem cells for tumor-free heart repair
J. Exp. Med., February 19, 2007; 204(2): 405 - 420.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
S. Yamada, G. C. Kane, A. Behfar, X.-K. Liu, R. B. Dyer, R. S. Faustino, T. Miki, S. Seino, and A. Terzic
Protection conferred by myocardial ATP-sensitive K+ channels in pressure overload-induced congestive heart failure revealed in KCNJ11 Kir6.2-null mutant
J. Physiol., December 15, 2006; 577(3): 1053 - 1065.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
G. C. Kane, C.-F. Lam, F. O'Cochlain, D. M. Hodgson, S. Reyes, X.-K. Liu, T. Miki, S. Seino, Z. S. Katusic, and A. Terzic
Gene knockout of the KCNJ8-encoded Kir6.1 KATP channel imparts fatal susceptibility to endotoxemia
FASEB J, November 1, 2006; 20(13): 2271 - 2280.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.