X-ray diffraction patterns from mammalian heart muscle

Matsubara, Ichiro; Millman, B. M.

doi:10.1016/0022-2836(74)90246-0

Cited by 68 publications

(57 citation statements)

References 27 publications

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“…During the period of relaxation between rhythmic contractions cross bridges lie close to the thin filaments, but the cross bridges are much closer to the thick filaments during prolonged relaxation in a quiescent heart (18). This phenomenon can be reproduced in skinned cardiac fibers by changing the Ca concentration (19).…”

Section: Discussionmentioning

confidence: 90%

“…The center to center distance between adjacent thick and thin filaments in intact myocytes from mammalian heart is approximately 23 nm (18). Using the dimensions of myosin and the positions of the center of mass and the site that attaches to actin from the x-ray crystallographic model of Rayment et al (16), one can estimate the relative change in distances between myosin and actin interacting sites that phosphorylation of MBP-C would produce in the filament lattice in the intact cell at physiological sarcomere length (Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Alteration of myosin cross bridges by phosphorylation of myosin-binding protein C in cardiac muscle.

Weisberg

Winegrad

1996

Proc. Natl. Acad. Sci. U.S.A.

171

149

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In addition to the contractile proteins actin and myosin, contractile filaments of striated muscle contain other proteins that are important for regulating the structure and the interaction of the two force-generating proteins. In the thin filaments, troponin and tropomyosin form a Ca-sensitive trigger that activates normal contraction when intracellular Ca is elevated. In the thick filament, there are several myosinbinding proteins whose functions are unclear. Among these is the myosin-binding protein C (MBP-C). The cardiac isoform contains four phosphorylation sites under the control of cAMP and calmodulin-regulated kinases, whereas the skeletal isoform contains only one such site, suggesting that phosphorylation in cardiac muscle has a specific regulatory function. We isolated natural thick filaments from cardiac muscle and, using electron microscopy and optical diffraction, determined the effect of phosphorylation of MBP-C on cross bridges. The thickness of the filaments that had been treated with protein kinase A was increased where cross bridges were present. No change occurred in the central bare zone that is devoid of cross bridges. The intensity of the reflections along the 43-nm layer line, which is primarily due to the helical array of cross bridges, was increased, and the distance of the first peak reflection from the meridian along the 43-nm layer line was decreased. The results indicate that phosphorylation of MBP-C (i) extends the cross bridges from the backbone of the filament and (ii) increases their degree of order and/or alters their orientation. These changes could alter rate constants for attachment to and detachment from the thin filament and thereby modify force production in activated cardiac muscle.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Alteration of myosin cross bridges by phosphorylation of myosin-binding protein C in cardiac muscle.

Weisberg

Winegrad

1996

Proc. Natl. Acad. Sci. U.S.A.

171

149

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“…35 Similarly, the interfilament lattice spacing is decreased by increasing SL in skinned (glycerinated) muscle. 36 Although the latter study was conducted using skeletal muscle, it is reasonable to assume that the result can be extended to skinned cardiac muscle.…”

Section: Discussionmentioning

confidence: 99%

Effects of MgADP on Length Dependence of Tension Generation in Skinned Rat Cardiac Muscle

Fukuda

Kajiwara

Ishiwata

et al. 2000

Circulation Research

102

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Abstract-The effect of MgADP on the sarcomere length (SL) dependence of tension generation was investigated using skinned rat ventricular trabeculae. Increasing SL from 1.9 to 2.3 m decreased the muscle width by Ϸ11% and shifted the midpoint of the pCa-tension relationship (pCa 50 ) leftward by about 0.2 pCa units. MgADP (0.1, 1, and 5 mmol/L) augmented maximal and submaximal Ca 2ϩ -activated tension and concomitantly diminished the SL-dependent shift of pCa 50 in a concentration-dependent manner. In contrast, pimobendan, a Ca 2ϩ sensitizer, which promotes Ca 2ϩ binding to troponin C (TnC), exhibited no effect on the SL-dependent shift of pCa 50 , suggesting that TnC does not participate in the modulation of SL-dependent tension generation by MgADP. At a SL of 1.9 m, osmotic compression, produced by 5% wt/vol dextran (molecular weight Ϸ464 000), reduced the muscle width by Ϸ13% and shifted pCa 50 leftward to a similar degree as that observed when increasing SL to 2.3 m. This favors the idea that a decrease in the interfilament lattice spacing is the primary mechanism for SL-dependent tension generation. MgADP (5 mmol/L) markedly attenuated the dextran-induced shift of pCa 50 , and the degree of attenuation was similar to that observed in a study of varying SL. The actomyosin-ADP complex (AM.ADP) induced by exogenous MgADP has been reported to cooperatively promote myosin attachment to the thin filament. We hereby conclude that the increase in the number of force-generating crossbridges on a decrease in the lattice spacing is masked by the cooperative effect of AM.ADP, resulting in depressed SL-dependent tension generation. The full text of this article is available at http://www.circresaha.org. This intrinsic ability of the heart to alter cardiac output forms the basis for the Frank-Starling law of the heart. It is well established that twitch tension and Ca 2ϩ responsiveness in cardiac muscle preparations are enhanced as muscle length (ie, sarcomere length [SL]) is increased within the normal physiological range (SL from Ϸ1.8 to Ϸ2.3 m). 1-5 Although a number of studies have been conducted to account for the SL dependence of tension generation in living myocardium, its mechanism has not been completely elucidated. 6 However, at the myofilament level, there is an increasing amount of evidence suggesting that the SL dependence is primarily due to a change in the interfilament lattice spacing that accompanies the SL change. 7-9 A possible consequence of the decreased lattice spacing is an increase in the probability of myosin attachment to the thin filament, resulting in an increase in the number of force-generating crossbridges. 7,10,11 Ishiwata and Oosawa 12 proposed a model based on the Ca 2ϩ -dependent flexibility of the thin filament, in which they assumed that (1) the muscle volume (ie, the lattice volume) remains constant on a change in SL and that (2) there is a critical distance between the thick and thin filaments for tension generation. This model quantitatively explains both the stretch-induced increas...

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“…Alterations in interfilament lattice spacing, such as increases in the lattice spacing as a result of shortening, leads to sarcomere thickening and intracellular volume redistribution (Elliott et al 1963(Elliott et al , 1967Brandt et al 1967). In turn, the developed active tension decreases via decreased approximation of myosin and actin filaments, and thus less strong binding cross-bridges are formed (Rome 1972;Matsubara and Millman 1974b). Although myocyte lengthening and subsequent lattice reduction are intimately linked, accumulating evidence suggests that lattice reduction itself does not play per se a major role in length-dependent cardiac muscle activation.…”

Section: Interfilament Lattice Spacing Versus Myocyte Lengtheningmentioning

confidence: 99%

Historical perspective on heart function: the Frank–Starling Law

Sequeira

Velden

2015

Biophys Rev

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More than a century of research on the FrankStarling Law has significantly advanced our knowledge about the working heart. The Frank-Starling Law mandates that the heart is able to match cardiac ejection to the dynamic changes occurring in ventricular filling and thereby regulates ventricular contraction and ejection. Significant efforts have been attempted to identify a common fundamental basis for the Frank-Starling heart and, although a unifying idea has still to come forth, there is mounting evidence of a direct relationship between length changes in individual constituents (cardiomyocytes) and their sensitivity to Ca 2+ ions. As the Frank-Starling Law is a vital event for the healthy heart, it is of utmost importance to understand its mechanical basis in order to optimize and organize therapeutic strategies to rescue the failing human heart. The present review is a historic perspective on cardiac muscle function. We Brevive^a century of scientific research on the heart's fundamental protein constituents (contractile proteins), to their assemblies in the muscle (the sarcomeres), culminating in a thorough overview of the several synergistically events that compose the Frank-Starling mechanism. It is the authors' personal beliefs that much can be gained by understanding the Frank-Starling relationship at the cellular and whole organ level, so that we can finally, in this century, tackle the pathophysiologic mechanisms underlying heart failure.

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X-ray diffraction patterns from mammalian heart muscle

Cited by 68 publications

References 27 publications

Alteration of myosin cross bridges by phosphorylation of myosin-binding protein C in cardiac muscle.

Alteration of myosin cross bridges by phosphorylation of myosin-binding protein C in cardiac muscle.

Effects of MgADP on Length Dependence of Tension Generation in Skinned Rat Cardiac Muscle

Historical perspective on heart function: the Frank–Starling Law

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