Changes In Sarcomere Length Research Articles

Mechanism of force enhancement during stretching of skeletal muscle fibres investigated by high time-resolved stiffness measurements

Stretching of active muscles leads to a great enhancement of the force developed without increased ATP consumption. The mechanism of force enhancement is still debated and it is not clear if it is due to increased crossbridge strain or to a stretch-induced increase in crossbridge number. The present study, performed on single fibres from tibialis anterior or interosseus muscles of the frog at 5 °C, was aimed at clarifying this point. A striation follower device was used to measure sarcomere length changes. Force was measured during the application of stretches (0.15-3.9 ms duration, 3-7.8 nm per half-sarcomere amplitude) to activated fibres. Small 4 kHz sinusoidal length oscillations, superimposed on the stretches, were used to calculate fibre stiffness with high time resolution. Stiffness increased during the stretch then subsequently decayed, all in parallel with tension. Likewise, during quick releases, stiffness decreased during the release then subsequently recovered in parallel with tension. Comparison of tension and stiffness both during the tetanus rise and also during stretches which doubled tension, imposed on the tetanus rise, indicated that stretch-induced crossbridge recruitment was only about 11 %, suggesting that force enhancement by stretching is mainly due to an increase of individual crossbridge force, whereas crossbridge recruitment plays only a minor role. The accompanying stiffness changes can be explained by non-linearity of myofilament compliance.

Effects of Nitrosation on Cardiac Myocyte Shortening

In the heart, there are two pathways for nitric oxide (NO) signaling, the classic cGMP-PKG and S-nitrosation of proteins. The nitrosation pathway involves an oxidation of cysteine thiols by nitrosonium NO+, and can therefore be a significant, reversible post-translational modification of proteins. Previous studies using NO donors such as S-nitroso-N-acetylpenicillamine (SNAP) were unable to resolve between to two pathways. We hypothesized that nitrosation is an important post-translational modifier of myocardial contractility. To test this hypothesis, we examined the effects of S-nitroso-L-cysteine (CysNO), a selective nitrosonium donor that is actively transported into the cell, on sarcomere shortening in unloaded mouse cardiac myocytes. Perfusion of cardiac myocytes with CysNO (30 μM) resulted in the reduction of sarcomere length changes by ∼80%. This period of blunted sarcomere length changes was followed by a ∼15 second exponential recovery in sarcomere length. During the recovery phase, the maximal velocities of shortening and re-lengthening were diminished. Our data suggest a possible in vivo role of NO+ in regulating myocardial contractility.

Elastic Energy Storage and Radial Forces in the Myofilament Lattice Depend on Sarcomere Length

We most often consider muscle as a motor generating force in the direction of shortening, but less often consider its roles as a spring or a brake. Here we develop a fully three-dimensional spatially explicit model of muscle to isolate the locations of forces and energies that are difficult to separate experimentally. We show the strain energy in the thick and thin filaments is less than one third the strain energy in attached cross-bridges. This result suggests the cross-bridges act as springs, storing energy within muscle in addition to generating the force which powers muscle. Comparing model estimates of energy consumed to elastic energy stored, we show that the ratio of these two properties changes with sarcomere length. The model predicts storage of a greater fraction of energy at short sarcomere lengths, suggesting a mechanism by which muscle function shifts as force production declines, from motor to spring. Additionally, we investigate the force that muscle produces in the radial or transverse direction, orthogonal to the direction of shortening. We confirm prior experimental estimates that place radial forces on the same order of magnitude as axial forces, although we find that radial forces and axial forces vary differently with changes in sarcomere length.

Modification of beef quality through steer age at slaughter, breed cross and growth promotants

Girard, I., Aalhus, J. L., Basarab, J. A., Larsen, I. L. and Bruce, H. L. 2012. Modification of beef quality through steer age at slaughter, breed cross and growth promotants. Can. J. Anim. Sci. 92: 175–188. A 23 factorial experiment tested the interactions of slaughter age (12–13 or 18–20 mo), growth implants use (Component E-S, TE-S), ractopamine hydrochloride (RAC) feed supplementation use and breed cross [Hereford–Aberdeen Angus (HAA) or Charolais–Red Angus (CRA)] on pH, temperature, objective colour measurements, relative myoglobin states, sarcomere lengths, shear force, and water losses of m. semitendinosus (ST) and m. gluteus medius (GM) from 112 crossbred steers. In the ST, age affected objective colour measurements by increasing chroma and decreasing lightness (L*) and hue angle (P<0.05). Metmyoglobin (MMB) content of the ST also increased with steer age (P<0.05). In the GM, yearling-fed steers had greater MMB content than calf-fed steers, while hue angle varied the opposite way (P<0.05). Other variations in meat colour and myoglobin contents were more complex in the GM than the ST as they involved three-way interactions between the different treatments. Shear force and purge loss of the ST increased with implantation (P<0.05) with no change in sarcomere length (P>0.05). Shear force standard deviation was similar for breed crosses when yearling-fed but greatest for CRA breed cross when calf-fed (P<0.05). In both muscles, purge loss was increased by RAC supplementation (P<0.05). RAC supplementation did not affect sarcomere length and shear force in both muscles (P>0.10). In the GM, shear force increased with age and with CRA genetics (P<0.05). Results indicated that producers seeking to reduce beef toughness should consider using British crossbreds, exclude the use of hormonal implants and slaughter process steers at 12 to13 mo of age.

Sunitinib causes dose‐dependent negative functional effects on myocardium and cardiomyocytes

To examine the acute effects of sunitinib on inotropic function, intracellular Ca(2+) transients, myofilament Ca(2+) sensitivity and generation of reactive oxygen species (ROS) in human multicellular myocardium and isolated mouse cardiomyocytes. To search for microRNAs as suitable biomarkers for indicating toxic cardiac effects. After exposure to sunitinib (0.1-10 µg/mL) developed force, diastolic tension and kinetic variables were assessed in isolated human myocardium. Changes in myocyte sarcomere length, whole-cell calcium transients, myofilament force-Ca(2+) relationship, and ROS generation were examined in isolated ventricular mouse cardiomyocytes. Microarray and realtime-PCR were used to screen for differentially expressed microRNAs in cultured cardiomyocytes that were exposed for 24 h to sunitinib. We found that higher concentrations of sunitinib (1 and 10 µg/mL) decreased developed force at 30 minutes 76.9 + 2.8 and 54.5 + 6.3%, compared to 96.1 + 2.6% in controls (P < 0.01). Sunitinib exposure significantly decreased sarcomere shortening and Ca2+ transients. Myofilament Ca(2+) sensitivity was not altered, while ROS levels were significantly increased after exposure to the drug. MicroRNA expression patterns were not altered by sunitinib. Sunitinib elicits a dose-dependent negative inotropic effect in myocardium, accompanied by a decline in intracellular Ca(2+) and increased ROS generation. In clinical practice, these cardiotoxic effects should be considered in cases where cardiac concentrations of sunitinib could be increased.

Length Dependent Activation Develops Virtually Instantaneously (&lt;5MS) in Guinea Pig Myocardium

Myofilament length dependent activation (LDA) is a universal property of striated muscle. The molecular mechanisms that underlie LDA are poorly understood. Additionally, the rate at which LDA appears following a change in sarcomere length (SL) is unknown. Accordingly, we compared sub-maximal activation (pCa 5.7;∼60%Fo) at steady state SL to sub-maximal activation following a rapid stretch to the same SL. Isolated skinned guinea-pig myofibrils were attached to glass micro-tools positioned on the stage of an inverted microscope (15C); one probe functioned as a force cantilever, while the other probe was attached to a rapid displacement generator; a Ca2+ pulse was applied by rapid translation of a double-barreled perfusion pipette (de Tombe, AJP, 2007). Activations were performed at SL=2.3µm (steady state), or after a rapid (5ms) stretch from SL=2.0µm. Steady state active force (62+2.8%) was similar to rapid stretch force (61+2.7%, respectively). Activation kinetics, measured as the time it takes for force to reach 50% of steady state force (T50), were also similar between steady state and rapid stretch (0.88+0.03s and 0.86+0.4s, respectively). Our data suggests that the transduction of the “length signal” in guinea-pig cardiac myofibrils occurs within 5 ms.

Effect of Confinement on Titin Conformation and Elasticity

Elasticity in muscle sarcomeres results largely from the mechanical properties of the giant protein titin. The I-band parts of titin molecules form filamentous connections between thick filaments and the Z-line, and behave as semi-flexible polymers, passively coiling and uncoiling during changes in sarcomere length. Important questions about titin mechanics in vivo concern effects of confinement, due to the surrounding actin filament lattice and to the high local concentration of titin. The actin lattice changes across the I-band, from hexagonal near the A-band to tetragonal towards the Z-line. At resting sarcomere length, a single hexagonal unit cell has radius ∼27 nm (Millman, 1998) and contains the six titin molecules that emerge from each thick filament, with a space of radius R ∼11 nm available to each molecule. The tetragonal lattice has average side length ∼24 nm and contains three titin molecules, with radius ∼7.8 nm for each molecule. Taking into account the condition for transition from weak to strong confinement 2R < RF (De Gennes, 1979), or 2R ∼ Lp (Cifra, 2009), and the average persistence length of titin (Lp, 9-19 nm), it can be concluded thatI-band titin is confined towards the Z-line. We analysed the effect of cylindrical confinement on the force-extension relationship of a polymer chain and showed it to lead to stiffening of the chain. This result, together with the above estimates, indicates that values of titin stiffness in situ derived from the interpolation formula for an unconfined worm-like chain (Marko & Siggia, 1995) are likely to be underestimates, even if titin molecules cross the I-band independently.

A theory on auto-oscillation and contraction in striated muscle

It is widely accepted that muscle cells take either force-generating or relaxing state in an all-or-none fashion through the so-called excitation–contraction coupling. On the other hand, the membrane-less contractile apparatus takes the third state, i.e., the auto-oscillation (SPOC) state, at the activation level that is intermediate between full activation and relaxation. Here, to explain the dynamics of all three states of muscle, we construct a novel theoretical model based on the balance of forces not only parallel but also perpendicular to the long axis of myofibrils, taking into account the experimental fact that the spacing of myofilament lattice changes with sarcomere length and upon contraction. This theory presents a phase diagram composed of several states of the contractile apparatus and explains the dynamic behavior of SPOC, e.g., periodical changes in sarcomere length with the saw-tooth waveform. The appropriate selection of the constant of the molecular friction due to the cross-bridge formation can explain the difference in the SPOC periods observed under various activating conditions and in different muscle types, i.e., skeletal and cardiac. The theory also predicts the existence of a weak oscillation state at the boundary between SPOC and relaxation regions in the phase diagram. Thus, the present theory comprehensively explains the characteristics of auto-oscillation and contraction in the contractile system of striated muscle.

The cellular force‐frequency response in ventricular myocytes from the varanid lizard, Varanus exanthematicus

To investigate the cellular mechanisms underlying the negative force‐frequency relationship in the ventricle of the varanid lizard, we measured sarcomere and cell shortening, intracellular Ca2+ ([Ca2+]i), action potentials (APs) and K+ currents in isolated ventricular myocytes. Experiments were conducted between 0.2–1.0 Hz, which spans the physiological range of heart rates at 20–22°C for this species. As frequency increased, diastolic length, percent change in sarcomere length and relaxation time decreased significantly. Shortening velocity was unchanged. The rate of rise of [Ca2+]i increased, [Ca2+]i transient amplitude decreased, and diastolic [Ca2+]i increased. The first order time constant of the [Ca2+]i transient decay decreased at higher frequencies, indicating frequency dependent acceleration of relaxation, then leveled out and did not change above 0.5 Hz. The AP rate of rise was unaffected, but the AP duration (APD) decreased with increasing frequency. Peak depolarization was only significantly decreased at 1.0 Hz. The decrease in APD was not due to changes in IKr or Ito. Our results suggest that a negative FFR in varanid lizard ventricle is caused by decreased amplitude of the [Ca2+]i transient with an increase in diastolic [Ca2+]i, leading to incomplete relaxation between beats at high frequencies. This coincides with shortened action potential duration (APD) at higher frequencies.

The cellular force-frequency response in ventricular myocytes from the varanid lizard, Varanus exanthematicus

To investigate the cellular mechanisms underlying the negative force-frequency relationship (FFR) in the ventricle of the varanid lizard, Varanus exanthematicus, we measured sarcomere and cell shortening, intracellular Ca(2+) ([Ca(2+)](i)), action potentials (APs), and K(+) currents in isolated ventricular myocytes. Experiments were conducted between 0.2 and 1.0 Hz, which spans the physiological range of in vivo heart rates at 20-22 degrees C for this species. As stimulation frequency increased, diastolic length, percent change in sarcomere length, and relaxation time all decreased significantly. Shortening velocity was unaffected. These changes corresponded to a faster rate of rise of [Ca(2+)](i), a decrease in [Ca(2+)](i) transient amplitude, and a seven-fold increase in diastolic [Ca(2+)](i). The time constant for the decay of the Ca(2+) transient (tau) decreased at higher frequencies, indicating a frequency-dependent acceleration of relaxation (FDAR) but then reached a plateau at moderate frequencies and did not change above 0.5 Hz. The rate of rise of the AP was unaffected, but the AP duration (APD) decreased with increasing frequency. Peak depolarization tended to decrease, but it was only significant at 1.0 Hz. The decrease in APD was not due to frequency-dependent changes in the delayed inward rectifier (I(Kr)) or the transient outward (I(to)) current, as neither appeared to be present in varanid ventricular myocytes. Our results suggest that a negative FFR relationship in varanid lizard ventricle is caused by decreased amplitude of the Ca(2+) transient coupled with an increase in diastolic Ca(2+), which leads to incomplete relaxation between beats at high frequencies. This coincides with shortened APD at higher frequencies.

Effect of pH and Electrostatic Interactions on Myofilament Lattice Volume

Changes interfilament lattice spacing is a major determinant of force production in striated muscle with reductions in force generation being observed with both expansion and compression of the lattice spacing relative to the normal physiological values. Previous studies have concluded that lattice spacing depends complexly on the balance of outward repulsive forces and inward attractive and compressive forces between thick and thin filaments. Since lattice spacing has important implications on force generation, we examined the effects of alterations in filament charge, induced by changes in intracellular pH (by the rapid application and withdrawal of 30 mM NH4Cl), on lattice spacing in intact twitching cardiac trabeculae. Since we observed changes in sarcomere length in response to changes in intracellular pH and since changes in sarcomere length induce changes in lattice spacing as a result of the isovolumic volume behavior of intact sarcomeres, sarcomere length was maintained at a fixed value (∼2.2 μm) during the pH interventions. Lattice spacing increased (p < 0.05) following NH4Cl wash in (measured after 5 minutes) when the pH is estimated to increase to ∼7.8 (Balnave 2000 J. Physiol.) to 36.9 +/-0.2. Following the washout of NH4Cl (which is estimated to decrease pH to ∼6.5 (Swietach 2005 J. Physiol.)) lattice spacing increased to 37.6+/−0.4 elevated above (P < 0.05) the space observed at control pH. Since the isoelectric point for myofilaments is ∼5 (Naylor, Biophys J, 1985), our findings suggest that, in addition to electrostatic, van der Waals' and osmotic forces, other pH-sensitive forces are also critical determinants of the lattice spacing, possibly the M-protein, myomesin or other M-line proteins which are postulated to hold thick filaments together in the M-band of striated muscle.

Activation and Relaxation Kinetics in Isolated Guinea-Pig Myofibrils: Impact of Sarcomere Length

Myofilament length dependent activation is a universal property of striated muscle that is most pronounced in myocardium. The mechanisms that underlie length dependency are incompletely understood. Accordingly, here we tested the hypothesis that sarcomere length (SL) affects the rate of force activation and/or force relaxation in response to a saturating pulse of Ca2+. Isolated skinned guinea-pig myofibrils were attached to glass micro-tools positioned on the stage of an inverted microscope (15 C); one probe functioned as a force probe cantilever, while the other probe was attached to a rapid displacement generator; the Ca2+ pulse was applied by rapid translation of a double-barreled perfusion pipette (de Tombe, AJP, 2007). Activations were performed at long (SL=2.06 ± 0.03 μm) and short (SL=1.85 ± 0.01; n=5) length. As expected, SL modulated maximum Ca2+ saturated force ∼20%. Both the rate of force redevelopment following a rapid release-restretch maneuver (kTr; ∼26%) and Ca2+ activated force development (kCa;∼14%) were faster at the long SL. In contrast, SL did not modulate any parameters of force relaxation following rapid removal of activator Ca2+. Our data suggest that length dependent myofilament activation in the heart may be the result of differential modulation of activation dynamics in response to changes in sarcomere length.

Tracking of Qdot Conjugated Titin Antibodies in Single Myofibril Stretch Experiments Reveals Ig-domain Unfolding at Physiological Sarcomere Lengths

The mechanical characteristics of titin in muscle sarcomeres were previously studied by us in single myofibril stretch experiments, where the extensibility of I-band titin segments was usually measured under static conditions. Here we investigated the behavior of I-band titin during and after stretch of single rabbit psoas myofibrils in real-time. The focus was on titin's proximal Ig-domain region, whose stretch dynamics were analyzed by labeling the myofibrils specifically in the N2A-titin domain using antibody-conjugated quantum dots, which stained the periphery of the myofibril but did not enter the myofilament lattice. Qdot labels were tracked to obtain the stretch-dependent change in epitope distance (across Z-disc) and sarcomere length (SL) over time. In contrast to what was expected from the current titin extensibility model, at sarcomere lengths of 2.5 and 3.8 μm, titin's proximal Ig-domain region elongated continuously, in proportion to the half I-band length. Already at ∼2.6 μm SL the proximal Ig-segment length exceeded the value expected if all Ig-domains remain folded. Our results suggest that Ig-domains unfold in parallel with PEVK-titin extension at physiological sarcomere lengths and under relatively low forces. By reducing the antibody-Qdot concentration, we succeeded in observing titin Ig-domain dynamics in myofibrils at the single-molecule level.

Automatic step-detection algorithm for analysis of sarcomere dynamics

Motile systems exhibit a stepwise nature, seen most prominently in muscle contraction. A novel algorithm has been developed that detects steps automatically in sarcomere-length change data and computes their size. The method is based on a nonlinear filter and a step detection protocol that detects local slope values in comparison to a threshold. The algorithm was first evaluated using artificial data with various degrees of Gaussian noise. Steps were faithfully detected even with significant noise. With actual data, the algorithm detected 2.7 nm steps and integer multiples thereof. The results confirm a quantal 2.7 nm step-size reported earlier. As stepwise phenomena become increasingly evident, automatic step-detection algorithms become increasingly useful since the limiting factor is almost always noise. The algorithm presented here offers a versatile and accurate tool that should be useful not only within muscle contraction and motility fields, but in fields which quantal phenomena play a role.

Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans

Sarcomeres are the basic contractile units of striated muscle. Our knowledge about sarcomere dynamics has primarily come from in vitro studies of muscle fibres and analysis of optical diffraction patterns obtained from living muscles. Both approaches involve highly invasive procedures and neither allows examination of individual sarcomeres in live subjects. Here we report direct visualization of individual sarcomeres and their dynamical length variations using minimally invasive optical microendoscopy to observe second-harmonic frequencies of light generated in the muscle fibres of live mice and humans. Using microendoscopes as small as 350 microm in diameter, we imaged individual sarcomeres in both passive and activated muscle. Our measurements permit in vivo characterization of sarcomere length changes that occur with alterations in body posture and visualization of local variations in sarcomere length not apparent in aggregate length determinations. High-speed data acquisition enabled observation of sarcomere contractile dynamics with millisecond-scale resolution. These experiments point the way to in vivo imaging studies demonstrating how sarcomere performance varies with physical conditioning and physiological state, as well as imaging diagnostics revealing how neuromuscular diseases affect contractile dynamics.

Review focus series: sarcomeric proteins as key elements in integrated control of cardiac function

Review and original articles in this focused issue of the Journal highlight the increased understanding of the role of sarcomeric proteins in control of cardiac function downstream of Ca2+ signalling. Figure 1 provides a context for integrating these articles in a minimal model of sarcomeric function in long- and short-term responses of the heart to stressors. In the model, state changes in the form of a physiological extrinsic stress, such as exercise or a pathophysiological stress such as hypertension promote a stream of mechanical and chemical signals, indicated as cytoskeletal, neurohormonal, and redox strains. Cytoskeletal strain induced by sarcomere length changes engage the Frank–Starling mechanism and also induce neurohormonal strains, as do feedback mechanisms. Readout of these neurohormonal signals is altered protein phosphorylation of cellular proteins including membrane proteins, transcription factors, and the sarcomeric proteins. Altered redox environment also induces post-translational modifications in sarcomeric proteins likely to trigger altered function independently of Ca2+ fluxes. Responses that compensate for the extrinsic stress maintain efficient cardiac function. For example, in exercise with increased venous return, rate and force of contraction and rate of relaxation are enhanced to match the increased heart rate and to permit cardiac output to increase with minimal increases in end-diastolic volume. A failure in the ability of the signalling cascade to engage compensatory pathways to maintain efficient function in response to an extrinsic stressor leads to decompensation and a viscous cycle ensues, exacerbating the stress. Figure 1 Scheme summarizing signalling mechanisms controlling cardiac function. See text for further description. Emerging evidence has substantially altered the understanding of the relative significance of mechanisms at the level of cardiac sarcomeric proteins in the processes summarized in Figure 1 . Sarcomeres are …

Serial casting in cerebral palsy: panacea, placebo, or peril?

Developmental Medicine & Child NeurologyVolume 49, Issue 10 p. 725-725 Free Access Serial casting in cerebral palsy: panacea, placebo, or peril? Martin Gough, Martin GoughSearch for more papers by this author Martin Gough, Martin GoughSearch for more papers by this author First published: 18 September 2007 https://doi.org/10.1111/j.1469-8749.2007.00725.xCitations: 7 See related article on page 781 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Shortland AP, Harris CA, Gough M, Robinson RO. (2002) Architecture of the medial gastrocnemius in children with spastic diplegia. Dev Med Child Neurol 44: 158– 163. 2 Tardieu C, Tabary JC, Tabary C, Huet de la Tour E (1977) Comparison of the sarcomere number adaptation in young and adult animals. Influence of tendon adaptation. J Physiologie 73: 1045– 1055. 3 Williams PE, Goldspink G. (1978) Changes in sarcomere length and physiological properties in immobilized muscle. J Anat 127: 459– 468. 4 Hof AL. (2003) Muscle mechanics and neuromuscular control. J Biomech 36: 1031– 1038. 5 Engsberg JR, Ross SA, Olree KS, Park TS. (2000) Ankle spasticity and strength in children with diplegic cerebral palsy. Dev Med Child Neurol 42: 42– 47. 6 Wiley ME, Damiano DL. (1998) Lower-extremity strength profiles in children with cerebral palsy. Dev Med Child Neurol 40: 100– 107. 7 Fry NR, Gough M, Shortland AP. (2004) Three-dimensional realisation of muscle morphology and architecture using ultrasound. Gait Posture 20: 177– 182. 8 Kerrigan DC, Riley PO, Rogan S, Burke DT. (2000) Compensatory advantages of toe-walking. Arch Phys Med Rehab 81: 38– 44. Citing Literature Volume49, Issue10October 2007Pages 725-725 ReferencesRelatedInformation

Muscle anatomy is a primary determinant of muscle relaxation dynamics in the lobster (Panulirus interruptus) stomatogastric system

We stained sarcomere thin filaments with fluorescently labeled phalloidin, measured sarcomere and muscle length, and calculated sarcomere number in pyloric and gastric mill muscles. A wide range of sarcomere lengths (3.25-12.29 microm), muscle lengths (5.9-21.1 mm), and sarcomere numbers (648-3,036) were observed. Sarcomere number differences occurred both because of changes in sarcomere length and muscle length, and sarcomere and muscle length varied independently. This independence, the wide range of sarcomere numbers present, and the muscles being all 'slow', graded muscles allowed us to use these data to test Huxley and Neidergerke's (1954) hypothesis that muscle dynamics depend on sarcomere number. The time constants of exponential fits to contraction relaxations were used to measure muscle dynamics, and comparison of theoretical predictions and experimental results quantitatively confirm the predicted dependence. The differing dynamics of the various pyloric muscles are likely functionally important, and the dependence of muscle dynamics on sarcomere number implies that sarcomere number is likely closely regulated in these muscles. The stomatogastric system may thus be an excellent model system for studying the mechanisms regulating muscle sarcomere number.

Exercise After Myocardial Infarction Improves Contractility and Decreases Myofilament Ca 2+ Sensitivity

See related article, pages 1079–1088 While myocardial infarction (MI) is the major cause of heart failure, there are conflicting data over the roles of abnormal calcium handling and myofilament function. The acute injury leads to the activation of neurohormones and cytokines, subsequent myocardial remodelling, further decline in heart function, and finally overt heart failure. Depressed myocyte contractility in the remodelled myocardium can largely be explained by Ca2+ handling abnormalities.1 Abnormalities in myofilament function are less well understood. A seminal study in pigs demonstrated that impaired pump function three weeks after MI can also be attributed to decreased maximal isometric tension in skinned cardiomyocytes in areas remote from the ischemic border zone.2 Somewhat paradoxically, the impairment occurred in the context of increased Ca2+ sensitivity of the myofilaments. The authors attributed the increased Ca2+ sensitivity following MI to reduced protein kinase A-mediated troponin I (TnI) phosphorylation.2 Increased myofilament Ca2+ sensitivity has also been reported for end-stage human heart failure, apparently largely because of a reduction of TnI phosphorylation.3 One of the most effective and least expensive therapies for cardiovascular disease is exercise. Clinical studies generally show a benefit of exercise training and a reduction of cardiac mortality after MI by 26%.4 The question remains of how soon to start exercising, especially after a large MI. In several clinical5 and animal6,7 studies, there were detrimental consequences when exercise began immediately after an MI. In the current issue of Circulation Research , de Waard et al8 present remarkable data addressing the question of exercise training early post MI. After a large MI, mice were subjected to 8 weeks of “voluntary” exercise training. Exercise had no detrimental effects on mortality and minimal effects on myocardial hypertrophy and left ventricular remodelling. Furthermore, there …

Sarcomere dynamics during muscular contraction and their implications to muscle function

This article attempts to identify the key aspects of sarcomere inhomogeneity and the dynamics of sarcomere length changes in muscle contraction experiments and focuses on understanding the mechanics of myofibrils or muscle fibres when viewed as independent units of biological motors (the half-sarcomeres) connected in series. Muscle force generation has been interpreted traditionally on the basis of the kinetics of crossbridge cycling, i.e. binding of myosin heads to actin and consecutive force generating conformational change of the head, under controlled conditions and assuming uniformity of sarcomere or half-sarcomere behaviour. However, several studies have shown that re-distribution of internal strain within myofibrils and muscle fibres may be a key player, particularly, during stretch or relaxation so that force kinetics parameters are strongly affected by sarcomere dynamics. Here, we aim to shed light on how force generation, crossbridge kinetics, and the complex sarcomere movements are to be linked and which mechanical concepts are necessary to develop a comprehensive contraction model of a myofibril.