Response of Equatorial X-Ray Reflections and Stiffness to Altered Sarcomere Length and Myofilament Lattice Spacing in Relaxed Skinned Cardiac Muscle

Martyn, Donald A.; Adhikari, Bishow; Regnier, Michael; Gu, Jie; Xu, Sengen; Yu, Linda Chia‐Hui

doi:10.1016/s0006-3495(04)74175-2

Cited by 37 publications

(56 citation statements)

References 51 publications

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“…In contrast, myofilament lattice spacing is a continuous inverse function of dextran concentration over that same concentration range. Our results are somewhat different from those of Martyn et al (21), who found, in rat skinned myocardium at 5°C, a proportional increase in I 1,1 /I 1,0 intensity ratio concomitant with a proportional decrease in interfilament spacing upon osmotic compression by application of dextran concentration up to 5% at short sarcomere length; at a longer sarcomere length, however, their data appear consistent with a saturation of the impact of osmotic compression on the I 1,1 /I 1,0 intensity ratio. The reason for this discrepancy is unclear but may be related to the large difference in temperature between these studies.…”

Section: Discussioncontrasting

confidence: 99%

“…These data, along with other data from our laboratories (16 -18), suggest that may we need to reexamine interfilament lattice spacing as a unifying hypothesis that explains all changes in myofilament calcium sensitivity. Recent experiments by Martyn et al (21) may lend some credence to this concept. These investigators demonstrated that an increase in either sarcomere length or externally applied osmotic pressure induces an increase in both the I 1,1 /I 1,0 intensity ratio and passive fiber stiffness, thus implicating an increase in the number of thin filament-associated cross-bridges under those conditions consistent with the aforementioned results of Yagi et al (37).…”

Section: "Lattice Spacing Hypothesis" Revisitedmentioning

confidence: 92%

“…Therefore, the question as to why murine skinned myocardium is more resistant to osmotic compression is unclear and requires further investigation. Likewise, Martyn et al (21) reported in skinned rat myocardium at 5°C that application of 1% dextran was without affect on either interfilament spacing or I 1,1 /I 1,0 intensity ratio at sacomere length of 2.0 and 2.35 m. Hence, the exact amount of dextran required to compress the myofilament lattice may depend on species, temperature, and, possibly, phosphorylation status of the contractile apparatus.…”

Section: Limitations Of Studymentioning

confidence: 94%

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Impact of osmotic compression on sarcomere structure and myofilament calcium sensitivity of isolated rat myocardium

Farman¹,

Walker²,

Tombe³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Farman, Gerrie P., John S. Walker, Pieter P. de Tombe, and Thomas C. Irving. Impact of osmotic compression on sarcomere structure and myofilament calcium sensitivity of isolated rat myocardium. Am J Physiol Heart Circ Physiol 291: H1847-H1855, 2006. First published June 2, 2006 doi:10.1152/ajpheart.01237.2005.-Changes in interfilament lattice spacing have been proposed as the mechanism underlying myofilament length-dependent activation. Much of the evidence to support this theory has come from experiments in which high-molecular-weight compounds, such as dextran, were used to osmotically shrink the myofilament lattice. However, whether interfilament spacing directly affects myofilament calcium sensitivity (EC50) has not been established. In this study, skinned isolated rat myocardium was osmotically compressed over a wide range (Dextran T500; 0 -6%), and EC50 was correlated to both interfilament spacing and I1,1/I1,0 intensity ratio. The latter two parameters were determined by X-ray diffraction in a separate group of skinned muscles. Osmotic compression induced a marked reduction in myofilament lattice spacing, concomitant with increases in both EC50 and I1,1/I1,0 intensity ratio. However, interfilament spacing was not well correlated with EC50 (r 2 ϭ 0.78). A much better and deterministic relationship was observed between EC50 and the I1,1/I1,0 intensity ratio (r 2 ϭ 0.99), albeit with a marked discontinuity at low levels of dextran compression; that is, a small amount of external osmotic compression (0.38 kPa, corresponding to 1% Dextran T500) produced a stepwise increase in the I1,1/I1,0 ratio concomitant with a stepwise decrease in EC50. These parameters then remained stable over a wide range of further applied osmotic compression (up to 6% dextran). These findings provide support for a "switch-like" activation mechanism within the cardiac sarcomere that is highly sensitive to changes in external osmotic pressure. skinned muscle; trabeculae; X-ray diffraction; dextran; osmotic pressure; myofilament length-dependent activation; regulation MYOFILAMENT LENGTH-DEPENDENT activation (LDA) is a phenomenon found in all striated muscle, but to varying extents, being a prominent feature of cardiac muscle (2,4,7,15,16) and the indirect flight muscle of insects (33) but is less prominent in skeletal muscle (17,26,32). LDA is defined as an increase in the amount of active force developed at longer sarcomere length for a given concentration of activating calcium ions. LDA is the underlying cellular mechanism that underlies the Frank-Starling law of the heart (16). This increase in myofilament calcium sensitivity is commonly measured by the EC 50 parameter, that is, the calcium concentration at which the active developed force is half that observed at a saturating calcium concentration. An understanding of the molecular mechanism(s) underlying LDA has remained elusive. A popular hypothetical mechanism for LDA is that changes in interfilament lattice spacing, usually estimated as changes in fiber width, are directly linke...

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Section: Discussioncontrasting

confidence: 99%

Section: "Lattice Spacing Hypothesis" Revisitedmentioning

confidence: 92%

Section: Limitations Of Studymentioning

confidence: 94%

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Impact of osmotic compression on sarcomere structure and myofilament calcium sensitivity of isolated rat myocardium

Farman¹,

Walker²,

Tombe³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…To explain length-dependent activation, it was proposed that the size of the thin filament regulatory units in the closed state is length dependent (22,36). Our results lend support to this latter hypothesis because they allow the development of a SL-dependent increase in force without apparent changes in cross-bridge kinetics.…”

Section: Discussionsupporting

confidence: 80%

Rate of tension redevelopment is not modulated by sarcomere length in permeabilized human, murine, and porcine cardiomyocytes

Czuriga

Csányi

Chłopicki

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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2ϩ sensitivity of isometric force development along with sarcomere length (SL) is considered as the basis of the FrankStarling law of the heart, possibly involving the regulation of crossbridge turnover kinetics. Therefore, the Ca 2ϩ dependencies of isometric force production and of the cross-bridge-sensitive rate constant of force redevelopment (k tr) were determined at different SLs (1.9 and 2.3 m) in isolated human, murine, and porcine permeabilized cardiomyocytes. k tr was also determined in the presence of 10 mM inorganic phosphate (Pi), which interfered with the force-generating cross-bridge transitions. The increases in Ca 2ϩ sensitivities of force with SL were very similar in human, murine, and porcine cardiomyocytes (⌬pCa 50: ϳ0.11). ktr was higher (P Ͻ 0.05) in mice than in humans or pigs at all Ca 2ϩ concentrations ([Ca 2ϩ ]) [maximum ktr (ktr,max) at a SL of 1.9 m and pCa 4.75: 1.33 Ϯ 0.11, 7.44 Ϯ 0.15, and 1.02 Ϯ 0.05 s Ϫ1 , in humans, mice, and pigs, respectively] but ktr did not depend on SL in any species. Moreover, when the ktr values for each species were expressed relative to their respective maxima, similar Ca 2ϩ dependencies were obtained. Ten millimolar Pi decreased force to ϳ60 -65% and left ⌬pCa 50 unaltered in all three species. P i increased ktr,max by a factor of ϳ1.6 in humans and pigs and by a factor of ϳ3 in mice, independent of SL. In conclusion, species differences exert a major influence on k tr, but SL does not appear to modulate the cross-bridge turnover rates in human, murine, and porcine hearts. mouse; pig; heart; skinned muscle; myofilament length-dependent activation; rate of tension redevelopment; calcium THE LENGTH-DEPENDENT INCREASE in myofilament Ca 2ϩ sensitivity is considered to be the explanation for the improved cardiac systolic performance following an increase in end-diastolic ventricular volume, i.e., for the Frank-Starling mechanism. Despite recent advances in the understanding of various aspects of the Frank-Starling mechanism (for a recent review, see Ref. 12), the molecular mechanism of the length-dependent Ca 2ϩ sensitization remains obscure. Ca 2ϩ regulates force production through changes in cross-bridge turnover kinetics in both the skeletal (4) and the cardiac (2, 44) muscle; accordingly, length-dependent alterations of cross-bridge transitions may well underlie the Frank-Starling law of the heart.Using rabbit skeletal muscle fibers, Zhao and Kawai (45) observed alterations in the rates of cross-bridge transitions during osmotic compression. These results were consistent with the length-dependent decrease in cross-bridge turnover and cross-bridge detachment at higher sarcomere length (SL), where lattice spacing was also reduced (45). However, in rat slow-twitch and rabbit fast-twitch skeletal muscle fibers the rate of tension redevelopment (k tr ), a measure of the rate of cross-bridge cycling, was reduced at short SL compared with a longer SL (24). In skinned rat cardiac trabeculae, simultaneous measurements of isometric force and rates of ATP consump...

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“…Changes in thin filament properties, such as substitution of ssTnI for cTnI (3,26,43) or point mutations in cTnC (29) and cTnT (5,6), as well as changes in thick filament properties (14) and factors affecting thin and thick filament interactions [lattice spacing (1,11,12,14,25,30,46), pH (13)] or the cross bridge cycle (10,23) have been all shown to influence the SL dependence of contraction. However, no single mechanism has emerged as the primary determinant of the Frank-Starling relationship.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Ca²⁺ binding of cardiac troponin reduces sarcomere length dependence of contractile activation independently of strong crossbridges

Korte

Feest

Razumova

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Calcium sensitivity of the force-pCa relationship depends strongly on sarcomere length (SL) in cardiac muscle and is considered to be the cellular basis of the Frank-Starling law of the heart. SL dependence may involve changes in myofilament lattice spacing and/or myosin crossbridge orientation to increase probability of binding to actin at longer SLs. We used the L48Q cardiac troponin C (cTnC) variant, which has enhanced Ca(2+) binding affinity, to test the hypotheses that the intrinsic properties of cTnC are important in determining 1) thin filament binding site availability and responsiveness to crossbridge activation and 2) SL dependence of force in cardiac muscle. Trabeculae containing L48Q cTnC-cTn lost SL dependence of the Ca(2+) sensitivity of force. This occurred despite maintaining the typical SL-dependent changes in maximal force (F(max)). Osmotic compression of preparations at SL 2.0 μm with 3% dextran increased F(max) but not pCa(50) in L48Q cTnC-cTn exchanged trabeculae, whereas wild-type (WT)-cTnC-cTn exchanged trabeculae exhibited increases in both F(max) and pCa(50). Furthermore, crossbridge inhibition with 2,3-butanedione monoxime at SL 2.3 μm decreased F(max) and pCa(50) in WT cTnC-cTn trabeculae to levels measured at SL 2.0 μm, whereas only F(max) was decreased with L48Q cTnC-cTn. Overall, these results suggest that L48Q cTnC confers reduced crossbridge dependence of thin filament activation in cardiac muscle and that changes in the Ca(2+) sensitivity of force in response to changes in SL are at least partially dependent on properties of thin filament troponin.

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Response of Equatorial X-Ray Reflections and Stiffness to Altered Sarcomere Length and Myofilament Lattice Spacing in Relaxed Skinned Cardiac Muscle

Cited by 37 publications

References 51 publications

Impact of osmotic compression on sarcomere structure and myofilament calcium sensitivity of isolated rat myocardium

Impact of osmotic compression on sarcomere structure and myofilament calcium sensitivity of isolated rat myocardium

Rate of tension redevelopment is not modulated by sarcomere length in permeabilized human, murine, and porcine cardiomyocytes

Enhanced Ca²⁺ binding of cardiac troponin reduces sarcomere length dependence of contractile activation independently of strong crossbridges

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Response of Equatorial X-Ray Reflections and Stiffness to Altered Sarcomere Length and Myofilament Lattice Spacing in Relaxed Skinned Cardiac Muscle

Cited by 37 publications

References 51 publications

Impact of osmotic compression on sarcomere structure and myofilament calcium sensitivity of isolated rat myocardium

Impact of osmotic compression on sarcomere structure and myofilament calcium sensitivity of isolated rat myocardium

Rate of tension redevelopment is not modulated by sarcomere length in permeabilized human, murine, and porcine cardiomyocytes

Enhanced Ca2+ binding of cardiac troponin reduces sarcomere length dependence of contractile activation independently of strong crossbridges

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Enhanced Ca²⁺ binding of cardiac troponin reduces sarcomere length dependence of contractile activation independently of strong crossbridges