AJP - Heart Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 280: H1653-H1659, 2001;
0363-6135/01 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 (16)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Baker, A. J.
Right arrow Articles by Conklin, B. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baker, A. J.
Right arrow Articles by Conklin, B. R.
Vol. 280, Issue 4, H1653-H1659, April 2001

Abnormal contraction caused by expression of Gi-coupled receptor in transgenic model of dilated cardiomyopathy

Anthony J. Baker1, Charles H. Redfern5, Mark D. Harwood1, Paul C. Simpson2,4, and Bruce R. Conklin2,3,5

Departments of Radiology,1  Medicine,2  and Pharmacology,3  Cardiovascular Research Institute,4  and Gladstone Institute of Cardiovascular Disease,5  University of California, San Francisco, California 94143

Although increased Gi signaling has been associated with dilated cardiomyopathy in humans, its role is not clear. Our goal was to determine the effects of chronically increased Gi signaling on myocardial function. We studied transgenic mice that expressed a Gi-coupled receptor (Ro1) that was targeted to the heart and regulated by a tetracycline-controlled expression system. Ro1 expression for 8 wk resulted in abnormal contractions of right ventricular muscle strips in vitro. Ro1 expression reduced myocardial force by >60% (from 35 ± 3 to 13 ± 2 mN/mm2, P < 0.001). Nevertheless, sensitivity to extracellular Ca2+ was enhanced. The extracellular [Ca2+] resulting in half-maximal force was lower with Ro1 expression compared with control (0.41 ± 0.05 vs. 0.88 ± 0.05 mM, P < 0.001). Ro1 expression slowed both contraction and relaxation kinetics, increasing the twitch time to peak (143 ± 6 vs. 100 ± 4 ms in control, P < 0.001) and the time to half relaxation (124 ± 6 vs. 75 ± 6 ms in control, P < 0.001). Increased pacing frequency increased contractile force threefold in control myocardium (P < 0.001) but caused no increase of force in Ro1-expressing myocardium. When stimulation was interrupted with rests, postrest force increased in control myocardium, but there was postrest decay of force in Ro1-expressing myocardium. These results suggest that defects in contractility mediated by Gi signaling may contribute to the development of dilated cardiomyopathy.

signaling; calcium; G proteins; mouse


This article has been cited by other articles:


Home page
 CirculationHome page
H. Ruan, S. Mitchell, M. Vainoriene, Q. Lou, L.-H. Xie, S. Ren, J. I. Goldhaber, and Y. Wang
Gi{alpha}1-Mediated Cardiac Electrophysiological Remodeling and Arrhythmia in Hypertrophic Cardiomyopathy
Circulation, August 7, 2007; 116(6): 596 - 605.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
L. Turnbull, H.-Z. Zhou, P. M. Swigart, S. Turcato, J. S. Karliner, B. R. Conklin, P. C. Simpson, and A. J. Baker
Sustained preconditioning induced by cardiac transgenesis with the tetracycline transactivator
Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1103 - H1109.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
D. T. McCloskey, L. Turnbull, P. M. Swigart, A. C. Zambon, S. Turcato, S. Joho, W. Grossman, B. R. Conklin, P. C. Simpson, and A. J. Baker
Cardiac transgenesis with the tetracycline transactivator changes myocardial function and gene expression
Physiol Genomics, June 16, 2005; 22(1): 118 - 126.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Morimoto, Q.-W. Lu, K. Harada, F. Takahashi-Yanaga, R. Minakami, M. Ohta, T. Sasaguri, and I. Ohtsuki
Ca2+-desensitizing effect of a deletion mutation Delta K210 in cardiac troponin T that causes familial dilated cardiomyopathy
PNAS, January 22, 2002; 99(2): 913 - 918.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online