In situ study of myofibrils, mitochondria and bound creatine kinases in experimental cardiomyopathies

Veksler, Vladimir; Ventura‐Clapier, Renée

doi:10.1007/978-1-4615-2612-4_19

Cited by 17 publications

(11 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our findings at pH 7.1 are also similar to most models of hypertrophy studied, which demonstrate similar calciumforce relationships. 26,27 Our experiments showed that reduction of pH from 7.1 to 6.8 decreased sensitivity to [Ca 2ϩ ] i without affecting F max . However, at a lower pH, 6.8, fibers from failing hearts demonstrated a significant decrease.…”

Section: Hajjar Et Al Human Myofilament Calcium Regulation 1681mentioning

confidence: 67%

Myofilament Calcium Regulation in Human Myocardium

et al. 2000

View full text Add to dashboard Cite

Background-We investigated whether decreased myofilament calcium contractile activation may, in part, contribute to heart failure. Methods and Results-Calcium concentration required for 50% activation and Hill coefficient for fibers from nonfailing and failing human hearts at pH 7.1 were not different. Maximum calcium-activated force (F max ) was also not different. However, at pH 6.8 and 6.9, differences were seen in myofilament calcium activation between nonfailing and failing hearts. At lower pH, failing myocardium was shifted left on the calcium axis compared with nonfailing myocardium, which suggested an increase in myofilament calcium responsiveness. Increased inorganic phosphate concentration decreased maximal force development by 56% in nonfailing and 36% in failing myocardium and shifted the calcium-force relationship by 2.01Ϯ0.22 versus 0.86Ϯ0.13 mol/L, respectively (PϽ0.05). Addition of cAMP resulted in a 0.56 mol/L shift toward higher intracellular calcium concentrations in nonfailing myocardium and a 1.04 mol/L shift in failing myocardium. Protein kinase A in the presence of cAMP resulted in a further rightward shift in nonfailing human myocardium but did not further shift the calcium-force relationship in fibers from failing hearts. cGMP also resulted in a greater decrease in myofilament calcium sensitivity in fibers from failing hearts. Conclusions-We propose that changes at the level of the thin myofilaments result in differential responses to changes in the intracellular milieu in nonfailing versus failing myocardium.

show abstract

Section: Hajjar Et Al Human Myofilament Calcium Regulation 1681mentioning

confidence: 67%

Myofilament Calcium Regulation in Human Myocardium

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Respiratory parameters of the total mitochondrial population were studied in situ in saponin permeabilized fibers using method of Veksler and Ventura‐Clapier (31) after 2 wk of HH. Fiber bundles (100‐250 μm in diameter) were excised from skeletal muscles after hindlimb suspension.…”

Section: Methodsmentioning

confidence: 99%

Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat

et al. 2011

View full text Add to dashboard Cite

Long-term spaceflight induces hypokinesia and hypodynamia, which, along microgravity per se, result in a number of significant physiological alterations, such as muscle atrophy, force reduction, insulin resistance, substrate use shift from fats to carbohydrates, and bone loss. Each of these adaptations could turn to serious health deterioration during the long-term spaceflight needed for planetary exploration. We hypothesized that resveratrol (RES), a natural polyphenol, could be used as a nutritional countermeasure to prevent muscle metabolic and bone adaptations to 15 d of rat hindlimb unloading. RES treatment maintained a net protein balance, soleus muscle mass, and soleus muscle maximal force contraction. RES also fully maintained soleus mitochondrial capacity to oxidize palmitoyl-carnitine and reversed the decrease of the glutathione vs. glutathione disulfide ratio, a biomarker of oxidative stress. At the molecular level, the protein content of Sirt-1 and COXIV in soleus muscle was also preserved. RES further protected whole-body insulin sensitivity and lipid trafficking and oxidation, and this was likely associated with the maintained expression of FAT/CD36, CPT-1, and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in muscle. Finally, chronic RES supplementation maintained the bone mineral density and strength of the femur. For the first time, we report a simple countermeasure that prevents the deleterious adaptations of the major physiological functions affected by mechanical unloading. RES could thus be envisaged as a nutritional countermeasure for spaceflight but remains to be tested in humans.

show abstract

“…This includes a decrease in the cytosolic free or bound MM‐CK and a dramatic drop in mi‐CK protein and activity that is linearly correlated with the severity of the reduction of CK flux (Zhang, 2002). Decreased mi‐CK coupling to oxidative phosphorylation has been consistently observed in animal models of cardiomyopathies of different origin and was suggested to be a marker of the transition between compensatory hypertrophy and failure (see Veksler & Ventura‐Clapier, 1994 for review and further references), suggesting a generalized loss of integration between cytosolic signals and mitochondria, and energy signalling impairment. This is responsible for the altered energy fluxes and the lower PCr/ATP ratio, and for the incapacity of the failing myocardium to adapt its energy production to energy utilization as well as to mobilize its contractile reserve (Ingwall, 1993; Liao et al 1996).…”

mentioning

confidence: 99%

Energy metabolism in heart failure

Ventura‐Clapier

Garnier

Veksler

2004

The Journal of Physiology

Self Cite

441

324

View full text Add to dashboard Cite

Heart failure (HF) is a syndrome resulting from the inability of the cardiac pump to meet the energy requirements of the body. Despite intensive work, the pathogenesis of the cardiac intracellular abnormalities that result from HF remains incompletely understood. Factors that lead to abnormal contraction and relaxation in the failing heart include metabolic pathway abnormalities that result in decreased energy production, energy transfer and energy utilization. Heart failure also affects the periphery. Patients suffering from heart failure always complain of early muscular fatigue and exercise intolerance. This is linked in part to intrinsic alterations of skeletal muscle, among which decreases in the mitochondrial ATP production and in the transfer of energy through the phosphotransfer kinases play an important role. Alterations in energy metabolism that affect both cardiac and skeletal muscles argue for a generalized metabolic myopathy in heart failure. Recent evidence shows that decreased expression of mitochondrial transcription factors and mitochondrial proteins are involved in mechanisms causing the energy starvation in heart failure. This review will focus on energy metabolism alterations in long-term chronic heart failure with only a few references to compensated hypertrophy when necessary. It will briefly describe the energy metabolism of normal heart and skeletal muscles and their alterations in chronic heart failure. It is beyond the scope of this review to address the metabolic switches occurring in compensated hypertrophy; readers could refer to well-documented reviews on this subject. Metabolic alterations in the heartSpecificity of cardiac metabolism. Myocardial function depends on a fine equilibrium between the work the heart has to perform to meet the requirements of the body and the energy that it is able to synthesize and transfer in the form of energy-rich phosphate bonds to sustain excitation-contraction coupling. Heart muscle is a highly oxidative tissue that produces more than 90% of its energy from mitochondrial respiration. Mitochondria occupy ≈30% of cardiomyocyte space and are well organized under the sarcolemma and in rows between myofilaments such that a constant diffusion distance exists between mitochondria and the core of myofilaments. During maximal exercise the heart uses more than 90% of its oxidative capacity, showing that there is no excess capacity of energy production over energy utilization (Mootha et al. 1997). There is a strict relationship in vitro and in vivo between oxygen consumption and cardiac work that occurs at constant global cellular ATP and phosphocreatine (PCr) concentrations. Therefore, a strong energy signalling pathways should exist to ensure a close matching between oxygen consumption and energy utilization. At present, the nature and function of such signals are still under debate. Oxygen availability, substrate limitation, ATP, ADP and PCr changes, inorganic phosphate, calcium, redox state and phosphotransfer systems have all been considered to play a ...

show abstract

In situ study of myofibrils, mitochondria and bound creatine kinases in experimental cardiomyopathies

Cited by 17 publications

References 73 publications

Myofilament Calcium Regulation in Human Myocardium

Myofilament Calcium Regulation in Human Myocardium

Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat

Energy metabolism in heart failure

Contact Info

Product

Resources

About