A100. A novel model for PKC activation and control of cardiac myofilament function

2006 ◽  
Vol 40 (6) ◽  
pp. 893-894
Author(s):  
J. Usprech ◽  
Q. Zhong ◽  
D.L. Aiello ◽  
G. La Rotta ◽  
W.G. Pyle
Keyword(s):  
Myofilament Function ◽  
Cardiac Myofilament ◽  
And Control ◽  
Novel Model ◽  
Pkc Activation

Caffeine alters cardiac myofilament activity and regulation independently of Ca2+ binding to troponin C

1995 ◽  
Vol 268 (6) ◽  
pp. C1348-C1353 ◽  
Author(s):  
F. M. Powers ◽  
R. J. Solaro
Keyword(s):  
Atpase Activity ◽  
Isometric Force ◽  
Troponin C ◽  
Fiber Bundles ◽  
Direct Effects ◽  
Skinned Fiber ◽  
Myofilament Function ◽  
Cardiac Myofilament ◽  
Myosin Interaction ◽  
Skinned Fiber Bundles

We investigated the mechanism by which caffeine influences myofilament responsiveness to Ca2+ by measuring isometric force, Ca2+ binding, and ATPase activity of dog cardiac myofilament proteins. Caffeine (20 mM) increased submaximal and depressed maximal force in skinned fiber bundles. Although the Ca2+ sensitivity of myofilament activity was increased by caffeine, there was no effect on Ca2+ binding to troponin C (TnC) in skinned fiber bundles. To determine if caffeine altered actin-myosin interaction or affected myosin directly, myofibrillar, actomyosin, and myosin ATPase activities were measured. Maximal Ca(2+)-activated myofibrillar Mg(2+)-ATPase activity was depressed by 20 mM caffeine, whereas submaximal Mg(2+)-ATPase activities were not changed. Actomyosin Mg(2+)-ATPase activity was significantly depressed by caffeine concentrations > or = 15 mM. Myosin Ca(2+)-ATPase activity was depressed by caffeine, whereas Mg(2+)-ATPase and K(EDTA)-ATPase activities were not affected. These data suggest that caffeine affects myofilament function via a mechanism that is independent of TnC-Ca2+ binding but that may involve direct effects on actin-cross-bridge interaction.

scholarly journals CONTROL NOVEL MODEL OF KNEE CPM DEVICE

2009 ◽  
Vol 12 (4) ◽  
pp. 18-29
Author(s):  
Thanh Diep Cong Tu
Keyword(s):  
Weight Ratio ◽  
Artificial Muscle ◽  
Network Control ◽  
Continuous Passive Motion ◽  
The Novel ◽  
Highly Nonlinear ◽  
Cord Injury ◽  
And Control ◽  
Novel Model ◽  
Interesting Alternative

In recent years, CPM - Continuous Passive Motion has been proved to be one of the most effective therapeutic methods for patients who have problems with motion such as spinal cord injury, ankle and knee injury, parkinson and so on. Many commercial CPM devices are found in market but all of them use motors as the main actuators. The lack of human compliance of electric actuators, which are commonly used in these machines, makes them potentially harmful to patients. An interesting alternative, to electric actuators for medical purposes, particularly promising for rehabilitation, is a pneumatic artificial muscle (PAM) actuator because of its high power/weight ratio and compliance properties. However, the highly nonlinear and hysteresis of PAM make it the challenging for design and control. In this study, a PID compensation using neural network control is studied to improve the control performance of the novel model of Knee CPM device.

scholarly journals ENerGetIcs in hypertrophic cardiomyopathy: traNslation between MRI, PET and cardiac myofilament function (ENGINE study)

2013 ◽  
Vol 21 (12) ◽  
pp. 567-571 ◽  
Author(s):  
A. Güçlü ◽  
T. Germans ◽  
E. R. Witjas-Paalberends ◽  
G. J. M. Stienen ◽  
W. P. Brouwer ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Myofilament Function ◽  
Cardiac Myofilament

Depressed cardiac myofilament function in human diabetes mellitus

2005 ◽  
Vol 289 (6) ◽  
pp. H2478-H2483 ◽  
Author(s):  
Eias E. Jweied ◽  
Ronald D. McKinney ◽  
Lori A. Walker ◽  
Irwin Brodsky ◽  
Alexander S. Geha ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Artery Bypass ◽  
Cardiac Cells ◽  
Hill Coefficient ◽  
Diabetic Patients ◽  
Human Diabetes ◽  
Myofilament Function ◽  
Cardiac Myofilament ◽  
Separate Control ◽  
Myocardial Biopsies

Diabetes mellitus is associated with a distinct cardiomyopathy. Whether cardiac myofilament function is altered in human diabetes mellitus is unknown. Myocardial biopsies were obtained from seven diabetic patients and five control, nondiabetic patients undergoing coronary artery bypass surgery. Myofilament function was assessed by determination of the developed force-Ca2+ concentration relation in skinned cardiac cells from flash-frozen human biopsies. Separate control experiments revealed that flash freezing of biopsy specimens did not affect myofilament function. All patients in the diabetes mellitus cohort were classified as Type 2 diabetes mellitus patients, and most showed signs of diastolic dysfunction. Diabetes mellitus was associated with depressed myofilament function, that is, decreased Ca2+ sensitivity (29%, P < 0.05 vs. control) and a trend toward reduction of maximum Ca2+-saturated force (29%, P = 0.08 vs. control). The slope of the force-Ca2+ concentration relation (Hill coefficient) was not affected by diabetes, however. We conclude that human diabetes mellitus is associated with decreased cardiac myofilament function. Depressed cardiac myofilament Ca2+ responsiveness may underlie the decreased ventricular function characteristic of human diabetic cardiomyopathy.

scholarly journals Pim-1 Kinase Phosphorylates Cardiac Troponin I and Regulates Cardiac Myofilament Function

2018 ◽  
Vol 45 (6) ◽  
pp. 2174-2186 ◽  
Author(s):  
Ni Zhu ◽  
Bing Yi ◽  
Zhifu Guo ◽  
Guanxin Zhang ◽  
Shengdong Huang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Cardiac Troponin I ◽  
Site Directed Mutagenesis ◽  
Functional Assay ◽  
Protective Effects ◽  
Diabetic Mice ◽  
Myofilament Function ◽  
Cardiac Myofilament

Background/Aims: Pim-1 is a serine/threonine kinase that is highly expressed in the heart, and exerts potent cardiac protective effects through enhancing survival, proliferation, and regeneration of cardiomyocytes. Its myocardial specific substrates, however, remain unknown. In the present study, we aim to investigate whether Pim-1 modulates myofilament activity through phosphorylation of cardiac troponin I (cTnI), a key component in regulating myofilament function in the heart. Methods: Coimmunoprecipitation and immunofluorescent assays were employed to investigate the interaction of Pim-1 with cTnI in cardiomyocytes. Biochemical, site directed mutagenesis, and mass spectrometric analyses were utilized to identify the phosphorylation sites of Pim1 in cTnI. Myofilament functional assay using skinned cardiac fiber was used to assess the effect of Pim1-mediated phosphorylation on cardiac myofilament activity. Lastly, the functional significance of Pim1-mediated cTnI in heart disease was determined in diabetic mice. Results: We found that Pim-1 specifically interacts with cTnI in cardiomyocytes and this interaction leads to Pim1-mediated cTnI phosphorylation, predominantly at Ser23/24 and Ser150. Furthermore, our functional assay demonstrated that Pim-1 induces a robust phosphorylation of cTnI within the troponin complex, thus leading to a decreased Ca2+ sensitivity. Insulin-like growth factor 1 (IGF-1), a peptide growth factor that has been shown to stimulate myocardial contractility, markedly induces cTnI phosphorylation at Ser23/24 and Ser150 through increasing Pim-1 expression in cardiomyocytes. In a high-fat diabetic mice model, the expression of Pim1 in the heart is significantly decreased, which is accompanied by a decreased phosphorylation of cTnI at Ser23/24 and Ser150, further implicating the pathological significance of the Pim1/cTnI axis in the development of diabetic cardiomyopathy. Conclusion: Our results demonstrate that Pim-1 is a novel kinase that phosphorylates cTnI primarily at Ser23/24 and Ser150 in cardiomyocytes, which in turn may modulate myofilament function under a variety of physiological and pathophysiological conditions.

scholarly journals Soluble Complement Receptor-1 Protects Heart, Lung, and Cardiac Myofilament Function From Cardiopulmonary Bypass Damage

Circulation ◽  
2000 ◽  
Vol 101 (5) ◽  
pp. 541-546 ◽  
Author(s):  
Paul J. Chai ◽  
Rashid Nassar ◽  
Annette E. Oakeley ◽  
Damian M. Craig ◽  
George Quick ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Complement Receptor ◽  
Myofilament Function ◽  
Cardiac Myofilament ◽  
Complement Receptor 1

Relaxin alters cardiac myofilament function through a PKC-dependent pathway

2009 ◽  
Vol 297 (1) ◽  
pp. H29-H36 ◽  
Author(s):  
Erynn E. Shaw ◽  
Philip Wood ◽  
Justyna Kulpa ◽  
Feng Hua Yang ◽  
Alastair J. Summerlee ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Troponin I ◽  
Troponin T ◽  
Immunoblot Analysis ◽  
Inotropic Effects ◽  
Myosin Binding Protein ◽  
Myofilament Function ◽  
Cardiac Myofilament ◽  
Intracellular Ca ◽  
Myofilament Activation

The pregnancy hormone relaxin (RLX) is a powerful cardiostimulatory peptide. Despite its well-characterized effects on the heart, the intracellular mechanisms responsible for RLX's positive inotropic effects are unknown. Cardiac myofilaments are the central contractile elements of the heart, and changes in the phosphorylation status of myofilament proteins are known to mediate changes in function. The first objective of this study was to determine whether RLX stimulates myofilament activation and alters the phosphorylation of one or more myofilament proteins. RLX works through a variety of intracellular signaling cascades in different tissue types. Protein kinases A (PKA) and C (PKC) are two common molecules implicated in RLX signaling and are known to affect myofilament function. Thus the second objective of this study was to determine whether RLX mediates its myocardial effects through PKA or PKC activation. Murine myocardium was treated with recombinant H2-RLX, and cardiac myofilaments were isolated. RLX increased cardiac myofilament force development at physiological levels of intracellular Ca2+ without altering myofilament ATP consumption. Myosin binding protein C, troponin T, and troponin I phosphorylation levels were increased with RLX treatment. Immunoblot analysis revealed an increase in myofilament-associated PKC-δ, decreases in PKC-α and -βII, but no effect on PKC-ε. Inhibition of PKC with chelerythrine chloride or PKC-δ with rottlerin prevented the RLX-dependent changes in myofilament function and protein phosphorylation. PKA antagonism with H-89 had no effect on the myofilament effects of RLX. This study is the first to show that RLX-dependent changes in myofilament-associated PKC alters myofilament activation in a manner consistent with its cardiostimulatory effects.

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