Myosin MgADP Release Rate Decreases as Sarcomere Length Increases in Skinned Rat Soleus Muscle Fibers

Fenwick, Axel J.; Leighton, Shelby R.; Tanner, Bertrand C.W.

doi:10.1016/j.bpj.2016.09.024

Cited by 11 publications

(17 citation statements)

References 62 publications

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“…4, C-D). Similar findings for these Ca 2þ -dependent detachment kinetics have been shown for human myocardial strips at physiological temperature (50), as well as rat cardiac and skeletal muscle measurements from our laboratory at subphysiological temperatures (23,36,51). These data suggest that Ca 2þ activation levels may influence cross-bridge detachment kinetics.…”

Section: Discussionsupporting

confidence: 85%

“…Previously, we observed slower rates of cross-bridge detachment at longer sarcomere length, with force also greater at the longer sarcomere length (23,36,51). We have largely interpreted these length-dependent differences to stem from strain-dependent differences in cross-bridge cycling, in which length-dependent tension increases led to slower detachment at longer sarcomere lengths because of slowed ADP dissociation rates (as the bridges bear greater strain and force).…”

Section: Discussionmentioning

confidence: 79%

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Omecamtiv Mecarbil Slows Myosin Kinetics in Skinned Rat Myocardium at Physiological Temperature

Kieu¹,

Awinda²,

Tanner

2019

Biophysical Journal

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Heart failure is a life-threatening condition that occurs when the heart muscle becomes weakened and cannot adequately circulate blood and nutrients around the body. Omecamtiv mecarbil (OM) is a compound that has been developed to treat systolic heart failure via targeting the cardiac myosin heavy chain to increase myocardial contractility. Biophysical and biochemical studies have found that OM increases calcium (Ca 2þ ) sensitivity of contraction by prolonging the myosin working stroke and increasing the actin-myosin cross-bridge duty ratio. Most in vitro studies probing the effects of OM on cross-bridge kinetics and muscle force production have been conducted at subphysiological temperature, even though temperature plays a critical role in enzyme activity and cross-bridge function. Herein, we used skinned, ventricular papillary muscle strips from rats to investigate the effects of [OM] on Ca 2þ -activated force production, cross-bridge kinetics, and myocardial viscoelasticity at physiological temperature (37 C). We find that OM only increases myocardial contractility at submaximal Ca 2þ activation levels and not maximal Ca 2þ activation levels. As [OM] increased, the kinetic rate constants for cross-bridge recruitment and detachment slowed for both submaximal and maximal Ca 2þ -activated conditions. These findings support a mechanism by which OM increases cardiac contractility at physiological temperature via increasing cross-bridge contributions to thin-filament activation as cross-bridge kinetics slow and the duration of cross-bridge attachment increases. Thus, force only increases at submaximal Ca 2þ activation due to cooperative recruitment of neighboring cross-bridges, because thin-filament activation is not already saturated. In contrast, OM does not increase myocardial force production for maximal Ca 2þ -activated conditions at physiological temperature because cooperative activation of thin filaments may already be saturated.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 79%

Omecamtiv Mecarbil Slows Myosin Kinetics in Skinned Rat Myocardium at Physiological Temperature

Kieu¹,

Awinda²,

Tanner

2019

Biophysical Journal

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“…30 Swimming training has several benefits to several organ systems of the human body and has been used primarily in the treatment of musculoskeletal disorders and prevention of diseases to improve muscle power and strength, flexibility, and agility. 31…”

Section: Discussionmentioning

confidence: 99%

Effects of physical training on sarcomere lengths and muscle-tendon interface of the cervical region in an experimental model of menopause

et al. 2019

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The aim of this study was to describe the structural and ultrastructural aspects of the myotendinous junction (MTJ) and the proximal and distal sarcomeres of the sternomastoid of aged Wistar rats subjected to an experimental model of menopause and swimming training. A total of 20 female elderly rats were divided into the following four groups (n=5 in each group): sedentary/no-menopausal (SNM), trained/no-menopausal (TNM), sedentary/menopausal (SM), and trained/menopausal (TM). The MTJ samples were dissected and analyzed using transmission electron microscopy. We showed that the TNM Group rats exhibited changes in morphological characteristics as a consequence of physical exercise, which included an increase of 36.60% (P<0.001) in the evagination length of the MTJ and a reduction in the length of the distal (77.38%) (P<0.0001) and proximal (68.15%) (P<0.0001) sarcomeres. The SM Group exhibited a reduction of about 275.93% (P<0.001) in the muscle-tendon interface and in the lengths of distal sarcomeres (55.87%) (P<0.0001) compared with SNM Group. Our results suggest that the swimming training under experimental model of menopause promoted tissue reorganization and increased muscle-tendon interaction with a drastic development in the length and thickness of the sarcoplasmatic invaginations and evaginations. In addition, the sarcomeres exhibited different lengths and a reduction in both groups subjected to swimming training.

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“…In addition, we observed realignment of the sarcomeres in series, increased length of distal and proximal sarcomeres, organization and parallel arrangement of the collagen bundles with increased lengths of sarcoplasmatic invaginations and evaginations (47% and 31.7%, respectively) which promoted the increase in their contact area. Fenwick, Leighton, and Tanner () report that skeletal muscle exhibits sarcomere length dependent variations in cross‐bridged kinetics and MgADP release. The actin‐myosin cross‐bridges use chemical energy from the MgATP hydrolysis to generate strength and shortening in striated muscle.…”

Section: Discussionmentioning

confidence: 99%

Myotendinous junction plasticity in aged ovariectomized rats submitted to aquatic training

Sierra

Fávaro

Cerri

et al. 2018

Microscopy Res & Technique

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The study aims to describe the tissue plasticity of MTJ through the morphological analysis of MTJ soleus in ovariectomized aged female Wistar rats submitted to aquatic training. Forty aged Wistar rats, 1 year and 2 months of age, were divided into four groups: sedentary (S), trained (T), ovariectomized (O), and trained/ovariectomized (OT). Employing the transmission electron microscopy, the ultrastructural and morphometric elements were revealed. In the S group, changes in morphological characteristics as a consequence of the aging process were seen, demonstrated by the conical shape of the muscle cell extremity, a large area with collagen deposit, and misalignment of sarcomeres in series. The T group presented ample adjustments when revealed the organization of MTJ, through the increase of the contact area and greater lengths of sarcoplasmatic invaginations and evaginations. The O group revealed extensive tissue disorganization with muscle atrophy, reduction of MTJ contact area, and consequently, changes in sarcoplasmatic invaginations and evaginations. The OT group demonstrated extensive remodeling with restructuring MTJ through the increase of tissue contact area, extensive organization, parallel arrangement, and increased length of sarcoplasmatic invaginations and evaginations. The distal sarcomeres presented higher lengths compared to the proximal sarcomeres in both the groups. We conclude that aquatic training was effective in the organization and structural remodeling of the myotendinous interface of ovariectomized aged rats. There was a greater area of contact, and consequently, greater resistance in the myotendinous interface promoting a lower predisposition to injuries.

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Myosin MgADP Release Rate Decreases as Sarcomere Length Increases in Skinned Rat Soleus Muscle Fibers

Cited by 11 publications

References 62 publications

Omecamtiv Mecarbil Slows Myosin Kinetics in Skinned Rat Myocardium at Physiological Temperature

Omecamtiv Mecarbil Slows Myosin Kinetics in Skinned Rat Myocardium at Physiological Temperature

Effects of physical training on sarcomere lengths and muscle-tendon interface of the cervical region in an experimental model of menopause

Myotendinous junction plasticity in aged ovariectomized rats submitted to aquatic training

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