scholarly journals The Super-Relaxed State and Length Dependent Activation in Porcine Myocardium

Author(s):  
Weikang Ma ◽  
Marcus Henze ◽  
Robert L Anderson ◽  
Henry M Gong ◽  
Fiona L Wong ◽  
...  

Rationale: Myofilament length dependent activation (LDA) is the key underlying mechanism of cardiac heterometric autoregulation, commonly referred as the Frank-Starling law of the heart. Although alterations in LDA are common in cardiomyopathic states, the precise structural and biochemical mechanisms underlying LDA remain unknown. Objective: Here, we examine the role of structural changes in the thick filament during diastole, in particular changes in the availability of myosin heads, in determining both calcium sensitivity and maximum contractile force during systole in permeabilized porcine cardiac fibers. Methods and Results: Permeabilized porcine fibers from ventricular myocardium were studied under relaxing conditions at short and long sarcomere length (SL) using muscle mechanics, biochemical measurements, and X-ray diffraction. Upon stretch, porcine myocardium showed the increased calcium sensitivity and maximum calcium activated force characteristic of LDA. Stretch increased diastolic ATP turnover, recruiting reserve myosin heads from the super-relaxed state (SRX) at longer SL. Structurally, X-ray diffraction studies in the relaxed-muscle confirmed a departure from the helical ordering of the thick-filament upon stretch which occurred concomitantly with a displacement of myosin heads towards actin, facilitating cross-bridge formation upon systolic activation. Mavacamten, a selective myosin-motor inhibitor known to weaken the transition to actin-bound power-generating states and to enrich the ordered SRX myosin population, reversed the structural effects of stretch on the thick-filament, blunting the mechanical consequences of stretch; mavacamten did not, however, prevent other structural changes associated with LDA in the sarcomere, such as decreased lattice spacing or troponin-displacement. Conclusions: Our findings strongly indicate that in ventricular muscle, LDA and its systolic consequences are dependent on the population of myosin heads competent to form cross-bridges and involves the recruitment of myosin heads from the reserve SRX pool during diastole.

2016 ◽  
Vol 113 (8) ◽  
pp. 2306-2311 ◽  
Author(s):  
Younss Ait-Mou ◽  
Karen Hsu ◽  
Gerrie P. Farman ◽  
Mohit Kumar ◽  
Marion L. Greaser ◽  
...  

The Frank–Starling mechanism of the heart is due, in part, to modulation of myofilament Ca2+ sensitivity by sarcomere length (SL) [length-dependent activation (LDA)]. The molecular mechanism(s) that underlie LDA are unknown. Recent evidence has implicated the giant protein titin in this cellular process, possibly by positioning the myosin head closer to actin. To clarify the role of titin strain in LDA, we isolated myocardium from either WT or homozygous mutant (HM) rats that express a giant splice isoform of titin, and subjected the muscles to stretch from 2.0 to 2.4 μm of SL. Upon stretch, HM compared with WT muscles displayed reduced passive force, twitch force, and myofilament LDA. Time-resolved small-angle X-ray diffraction measurements of WT twitching muscles during diastole revealed stretch-induced increases in the intensity of myosin (M2 and M6) and troponin (Tn3) reflections, as well as a reduction in cross-bridge radial spacing. Independent fluorescent probe analyses in relaxed permeabilized myocytes corroborated these findings. X-ray electron density reconstruction revealed increased mass/ordering in both thick and thin filaments. The SL-dependent changes in structure observed in WT myocardium were absent in HM myocardium. Overall, our results reveal a correlation between titin strain and the Frank–Starling mechanism. The molecular basis underlying this phenomenon appears not to involve interfilament spacing or movement of myosin toward actin but, rather, sarcomere stretch-induced simultaneous structural rearrangements within both thin and thick filaments that correlate with titin strain and myofilament LDA.


2014 ◽  
Vol 70 (a1) ◽  
pp. C94-C94
Author(s):  
Pawel Kuczera ◽  
Walter Steurer

The structure of d(ecagonal)-Al-Cu-Rh has been studied as a function of temperature by in-situ single-crystal X-ray diffraction in order to contribute to the discussion on energy or entropy stabilization of quasicrystals (QC) [1]. The experiments were performed at 293 K, 1223 K, 1153 K, 1083 K, and 1013 K. A common subset of 1460 unique reflections was used for the comparative structure refinements at each temperature. The results obtained for the HT structure refinements of d-Al-Cu-Rh QC seem to contradict a pure phasonic-entropy-based stabilization mechanism [2] for this QC. The trends observed for the ln func(I(T1 )/I(T2 )) vs.|k⊥ |^2 plots indicate that the best on-average quasiperiodic order exists between 1083 K and 1153 K, however, what that actually means is unclear. It could indicate towards a small phasonic contribution to entropy, but such contribution is not seen in the structure refinements. A rough estimation of the hypothetic phason instability temperature shows that it would be kinetically inaccessible and thus the phase transition to a 12 Å low T structure (at ~800 K) is most likely not phason-driven. Except for the obvious increase in the amplitude of the thermal motion, no other significant structural changes, in particular no sources of additional phason-related configurational entropy, were found. All structures are refined to very similar R-values, which proves that the quality of the refinement at each temperature is the same. This suggests, that concerning the stability factors, some QCs could be similar to other HT complex intermetallic phases. The experimental results clearly show that at least the ~4 Å structure of d-Al-Cu-Rh is a HT phase therefore entropy plays an important role in its stabilisation mechanism lowering the free energy. However, the main source of this entropy is probably not related to phason flips, but rather to lattice vibrations, occupational disorder unrelated to phason flips like split positions along the periodic axis.


2003 ◽  
Vol 802 ◽  
Author(s):  
R. G. Haire ◽  
S. Heathman ◽  
T. Le Bihan ◽  
A. Lindbaum ◽  
M. Iridi

ABSTRACTOne effect of pressure on elements and compounds is to decease their interatomic distances, which can bring about dramatic perturbations in their electronic nature and bonding, which can be reflected in changes in physical and/or chemical properties. One important issue in the actinide series of elements is the effect of pressure on the 5f-electrons. We have probed changes in electronic behavior with pressure by monitoring structure by X-ray diffraction, and have studied several actinide metals and compounds from thorium through einsteinium. These studies have employed angle dispersive diffraction using synchrotron radiation, and energy dispersive techniques via conventional X-ray sources. The 5f-electrons of actinide metals and their alloys are often affected significantly by pressure, while with compounds, the structural changes are often not linked to the involvement of 5 f-electron. We shall present some of our more recent findings from studies of selected actinide metals, alloys and compounds under pressure. A discussion of the results in terms of the changes in electronic configurations and bonding with regard to the element's position in the series is also addressed.


2005 ◽  
Vol 38 (5) ◽  
pp. 749-756 ◽  
Author(s):  
Ulrich Gesenhues

The polygonization of 200 nm rutile crystals during dry ball-milling at 10gwas monitored in detail by means of transmission electron microscopy (TEM) and X-ray diffraction (XRD). The TEM results showed how to modify the Williamson–Hall method for a successful evaluation of crystal size and microstrain from XRD profiles. Macrostrain development was determined from the minute shift of the most intense reflection. In addition, changes in pycnometrical density were monitored. Accordingly, the primary crystal is disintegrated during milling into a mosaic of 12–35 nm pieces where the grain boundaries induce up to 1.2% microstrain in a lower layer of 6 nm thickness. Macrostrain in the interior of the crystals rises to 0.03%. The pycnometrical density, reflecting the packing density of atoms in the grain boundary, decreases steadily by 1.1%. The results bear relevance to our understanding of plastic flow and the mechanism of phase transitions of metal oxides during high-energy milling.


Metals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 800
Author(s):  
Vladimír Girman ◽  
Maksym Lisnichuk ◽  
Daria Yudina ◽  
Miloš Matvija ◽  
Pavol Sovák ◽  
...  

In the present study, the effect of wet mechanical alloying (MA) on the glass-forming ability (GFA) of Co43Fe20X5.5B31.5 (X = Ta, W) alloys was studied. The structural evolution during MA was investigated using high-energy X-ray diffraction, X-ray absorption spectroscopy, high-resolution transmission electron microscopy and magnetic measurements. Pair distribution function and extended X-ray absorption fine structure spectroscopy were used to characterize local atomic structure at various stages of MA. Besides structural changes, the magnetic properties of both compositions were investigated employing a vibrating sample magnetometer and thermomagnetic measurements. It was shown that using hexane as a process control agent during wet MA resulted in the formation of fully amorphous Co-Fe-Ta-B powder material at a shorter milling time (100 h) as compared to dry MA. It has also been shown that substituting Ta with W effectively suppresses GFA. After 100 h of MA of Co-Fe-W-B mixture, a nanocomposite material consisting of amorphous and nanocrystalline bcc-W phase was synthesized.


Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1034
Author(s):  
Oladipo Folorunso ◽  
Yskandar Hamam ◽  
Rotimi Sadiku ◽  
Suprakas Sinha Ray ◽  
Neeraj Kumar

In this study, a hybrid of graphene nanoplatelets with a polypyrrole having 20 wt.% loading of carbon-black (HGPPy.CB20%), has been fabricated. The thermal stability, structural changes, morphology, and the electrical conductivity of the hybrids were investigated using thermogravimetric analyzer, differential scanning calorimeter, X-ray diffraction analyzer, scanning electron microscope, and laboratory electrical conductivity device. The morphology of the hybrid shows well dispersion of graphene nanoplatelets on the surface of the PPy.CB20% and the transformation of the gravel-like PPy.CB20% shape to compact spherical shape. Moreover, the hybrid’s electrical conductivity measurements showed percolation threshold at 0.15 wt.% of the graphene nanoplatelets content and the curve is non-linear. The electrical conductivity data were analyzed by comparing different existing models (Weber, Clingerman and Taherian). The results show that Taherian and Clingerman models, which consider the aspect ratio, roundness, wettability, filler electrical conductivity, surface interaction, and volume fractions, closely described the experimental data. From these results, it is evident that Taherian and Clingerman models can be modified for better prediction of the hybrids electrical conductivity measurements. In addition, this study shows that graphene nanoplatelets are essential and have a significant influence on the modification of PPy.CB20% for energy storage applications.


2017 ◽  
Vol 19 (31) ◽  
pp. 20867-20880 ◽  
Author(s):  
David C. Bock ◽  
Christopher J. Pelliccione ◽  
Wei Zhang ◽  
Janis Timoshenko ◽  
K. W. Knehr ◽  
...  

Crystal and atomic structural changes of Fe3O4upon electrochemical (de)lithiation were determined.


2002 ◽  
Vol 411 (2) ◽  
pp. 234-239 ◽  
Author(s):  
M Hecker ◽  
W Pitschke ◽  
D Tietjen ◽  
C.M Schneider

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