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

2001 ◽  
Vol 280 (4) ◽  
pp. H1653-H1659 ◽  
Author(s):  
Anthony J. Baker ◽  
Charles H. Redfern ◽  
Mark D. Harwood ◽  
Paul C. Simpson ◽  
Bruce R. Conklin
Keyword(s):  
Transgenic Mice ◽  
Right Ventricular ◽  
Dilated Cardiomyopathy ◽  
Myocardial Function ◽  
Expression System ◽  
Contractile Force ◽  
Ventricular Muscle ◽  
Time To Peak ◽  
Contraction And Relaxation

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.

Simulated ischemia and intracellular pH in isolated ventricular muscle

1989 ◽  
Vol 257 (2) ◽  
pp. C365-C376 ◽  
Author(s):  
B. Vanheel ◽  
L. Leybaert ◽  
A. De Hemptinne ◽  
I. Leusen
Keyword(s):  
Intracellular Ph ◽  
Time Course ◽  
Contractile Force ◽  
Rapid Decline ◽  
Control Value ◽  
Time To Peak ◽  
Simulated Ischemia ◽  
Buffering Power ◽  
Vitro Model

Isolated guinea pig papillary muscles were subjected to an in vitro model of ischemia, consisting of superfusion arrest and immersion in paraffin oil, which results in restriction of substrate supply and metabolite washout. Intracellular pH (pHi) and surface pH (pHs) were measured with glass microelectrodes. Contractile force declined to 82% of the pre-“ischemic” value after 2 min and to 37% of the control value after 10 min. In addition, a shortening of the time to peak and duration of contraction was noted. The rate of force development decreased later than the rate of relaxation. After 10 min, pHi was acidified on average 0.08 pH unit, which is about one-third of the measured pHs change. Tripling the ischemic pHi change by reduction of the intracellular buffering power only slightly increased the rate of tension decline. Experimental pHi changes of similar magnitude, induced during normal superfusion, had a smaller effect on contractile force and failed to reproduce the characteristic changes in time course of the contraction. It is concluded that, in our condition of simulated ischemia, the intracellular acidification cannot account fully for the rapid decline in contractility.

scholarly journals Conditional Expression of a Glucocorticoid Receptor Transgene in Thymocytes Reveals a Role for Thymic-Derived Glucocorticoids in Thymopoiesis in Vivo

Endocrinology ◽  
2005 ◽  
Vol 146 (6) ◽  
pp. 2501-2507 ◽  
Author(s):  
Ahmad Pazirandeh ◽  
Mikael Jondal ◽  
Sam Okret
Keyword(s):  
Transgenic Mice ◽  
Organ Culture ◽  
Expression System ◽  
Thymic Epithelial Cells ◽  
Inducible Expression System ◽  
Conditional Expression ◽  
Thymocyte Apoptosis ◽  
Antagonist Ru486

Abstract We and others have previously reported that thymic epithelial cells produce glucocorticoids (GCs). In vitro studies have also suggested that thymic-derived GCs play a role in the development of thymocytes. However, until now it has not yet been established whether thymic-derived GCs play a role in thymopoiesis in vivo. To investigate this, we conditionally overexpressed the GC receptor (GR) in thymocytes using transgenic mice with a tetracycline-inducible expression system. The influence of systemic GCs was excluded by adrenalectomizing the transgenic mice before the GR induction. Conditional expression of transgenic GR in the thymocytes of adrenalectomized transgenic mice led to a decrease in the thymocyte number. This was associated with increased thymocyte apoptosis. The effect of thymic-derived GCs on the thymocytes was confirmed after transgenic GR induction in a thymic organ culture system. Finally, the GR antagonist RU486 increased thymocyte number in adrenalectomized mice in vivo and prevented a reduction in thymocyte number in thymic organ culture after transgenic GR induction. These observations further confirmed a role for the thymic-derived GCs in regulating thymocyte homeostasis in vivo.

Studies on Ultrastructure and Cytochemistry of Right Ventricular Endomyocardial Biopsy

1990 ◽  
Vol 48 (3) ◽  
pp. 256-257
Author(s):  
Xia Mingyu ◽  
Ma Wengshu ◽  
Wu Xiangh ◽  
Chen Dong
Keyword(s):  
Light Microscopy ◽  
Right Ventricular ◽  
Dilated Cardiomyopathy ◽  
Endomyocardial Biopsy ◽  
Heart Diseases ◽  
Ultrastructural Localization ◽  
Controlled Study ◽  
Myocardial Biopsy ◽  
Morphological Assessment ◽  
Rheumatic Heart

This paper describes morphological and cytochemistry changes of endomyocardial biopsy in 94 patients. The samples of myoicardium were taken from 32 patients with dilated cardiomyopathy, and sdudied with light and electron microscop. The cytochemical studies in some of these patients were performed at histological and ultrastructure level. This paper also reported the result of myocardial biopsy in 33 patients with serious dysrythmia.The result of this controlled study indicates that morphological assessment in both cardiomyopathy and congenital or rheumatic heart diseases showed no special changes. In patients of dilated cardiomyopathy, the decreased activity of myosin ATPase was secondary to cardial failure. The change of succinate dehydrogenase (SDHase) was not significant with light microscopy. But ultrastructural localization of SDHase activity is valuable. Its activity was found to be localized in endomembrane and ridge of the mitochondria, the activity of this enzyme was decrease, normal, or increase. SDHase activity was more intense in cardial myocytes well-functioning, or ultrastructurally well preserved hearts.

Sign in / Sign up

Export Citation Format

Share Document