Dietary Nitrate and Skeletal Muscle Contractile Function in Heart Failure

Type 2 diabetes is characterized by reduced contractile force production and increased fatigability of skeletal muscle. While the maintenance of Ca2+ homeostasis during muscle contraction is a requisite for optimal contractile function, the mechanisms underlying muscle contractile dysfunction in type 2 diabetes are unclear. Here, we investigated skeletal muscle contractile force and Ca2+ flux during contraction and pharmacological stimulation in type 2 diabetic model mice ( db/db mice). Furthermore, we investigated the effect of treadmill exercise training on muscle contractile function. In male db/db mice, muscle contractile force and peak Ca2+ levels were both lower during tetanic stimulation of the fast-twitch muscles, while Ca2+ accumulation was higher after stimulation compared with control mice. While 6 wk of exercise training did not improve glucose tolerance, exercise did improve muscle contractile dysfunction, peak Ca2+ levels, and Ca2+ accumulation following stimulation in male db/db mice. These data suggest that dysfunctional Ca2+ flux may contribute to skeletal muscle contractile dysfunction in type 2 diabetes and that exercise training may be a promising therapeutic approach for dysfunctional skeletal muscle contraction. NEW & NOTEWORTHY The purpose of this study was to examine muscle contractile function and Ca2+ regulation as well as the effect of exercise training in skeletal muscle in obese diabetic mice ( db/db). We observed impairment of muscle contractile force and Ca2+ regulation in a male type 2 diabetic animal model. These dysfunctions in muscle were improved by 6 wk of exercise training.

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Effects of Regular Exercise Training on Skeletal Muscle Contractile Function

American Journal of Physical Medicine & Rehabilitation ◽

10.1097/01.phm.0000059336.40487.9c ◽

2003 ◽

Vol 82 (4) ◽

pp. 320-331 ◽

Cited By ~ 23

Author(s):

Robert H. Fitts

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Contractile Function ◽

Regular Exercise ◽

Muscle Contractile

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Abstract 1102: Cardiac-Specific Myosin Light Chain Kinase (MLCK), a Third Member of MLCK Family, Potentiates Sarcomere Formation and Cardiac Contraction

Circulation ◽

10.1161/circ.116.suppl_16.ii_221-a ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Jason Y Chan ◽

Morihiko Takeda ◽

Laura E Briggs ◽

Jonathan T Lu ◽

Nobuo Horikoshi ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Smooth Muscle ◽

Cardiac Hypertrophy ◽

Light Chain ◽

Myosin Light Chain Kinase ◽

Myosin Light Chain ◽

Contractile Function ◽

Severe Heart Failure ◽

Cardiac Contraction

Background: Two myosin light chain kinase (MLCK) proteins, skeletal (encoded by mylk2 gene) and smooth muscle MLCK (encoded by mylk1 gene) have been shown to be expressed in mammals. Human mylk2 has been mapped as a disease locus for familial cardiac hypertrophy (OMIM 606566 ), suggesting that abnormal function of skeletal MLCK stimulates cardiac hypertrophy. While phosphorylation of the putative substrate of skeletal MLCK, myosin light chain 2 (MLC2), is recognized as a key regulator of cardiac contraction, the abundance of skeletal MLCK in the heart is controversial, suggesting the existence of an additional MLCK that is preferentially expressed in cardiac muscle. Methods and Results: We characterized a new kinase named cardiac MLCK that is encoded by a gene homologous to mylk1 and 2 and is specifically expressed in the heart in both atrium and ventricle. Expression of cardiac MLCK was highly regulated by the cardiac homeobox transcription factor, Nkx2.5, in neonatal cardiomyocytes. The overall structure of cardiac MLCK protein is conserved with skeletal and smooth muscle MLCK including putative catalytic and adjacent Ca2+/calmodulin binding domains at the carboxyl-terminus. The amino-terminus is unique without significant homology to other known proteins. Cardiac MLCK phosphorylated MLC2v with a catalytic value of Km=4.3 micro M (Lineweaver-Burk analysis) indicating high affinity of cardiac MLCK to MLC2v, similar to the affinity of skeletal muscle MLCK to skeletal muscle MLC2 and smooth muscle MLCK to smooth muscle MLC2. Adenoviral-mediated overexpression of cardiac MLCK and knockdown of cardiac MLCK using RNAi in cultured cardiomyocytes revealed that cardiac MLCK regulates MLC2v phosphorylation, sarcomere organization and cardiac myocyte contraction. Expression of cardiac MLCK protein was significantly decreased in severe heart failure in vivo (post-myocardial infarction heart failure mouse model). Conclusion: Cardiac MLCK is a new key regulator of cardiac contraction and sarcomere organization. Reduction of cardiac MLCK function leading to decreased phosphorylation of MLC2v may contribute to compromised contractile function in the failing heart.

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Effects of fasting on isolated murine skeletal muscle contractile function during acute hypoxia

PLoS ONE ◽

10.1371/journal.pone.0225922 ◽

2020 ◽

Vol 15 (4) ◽

pp. e0225922

Author(s):

Cameron A. Schmidt ◽

Emma J. Goldberg ◽

Tom D. Green ◽

Reema R. Karnekar ◽

Jeffrey J. Brault ◽

...

Keyword(s):

Skeletal Muscle ◽

Contractile Function ◽

Acute Hypoxia ◽

Murine Skeletal Muscle ◽

Muscle Contractile

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Does Phototherapy Enhance Skeletal Muscle Contractile Function and Postexercise Recovery? A Systematic Review

Journal of Athletic Training ◽

10.4085/1062-6050-48.1.12 ◽

2013 ◽

Vol 48 (1) ◽

pp. 57-67 ◽

Cited By ~ 72

Author(s):

Paul A. Borsa ◽

Kelly A. Larkin ◽

Jerry M. True

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Contractile Function ◽

Placebo Control ◽

Original Research ◽

Data Sets ◽

Electromyographic Activity ◽

Postexercise Recovery ◽

Exercise Induced ◽

Muscle Contractile

Context Recently, researchers have shown that phototherapy administered to skeletal muscle immediately before resistance exercise can enhance contractile function, prevent exercise-induced cell damage, and improve postexercise recovery of strength and function. Objective To critically evaluate original research addressing the ability of phototherapeutic devices, such as lasers and light-emitting diodes (LEDs), to enhance skeletal muscle contractile function, reduce exercise-induced muscle fatigue, and facilitate postexercise recovery. Data Sources We searched the electronic databases PubMed, SPORTDiscus, Web of Science, Scopus, and Rehabilitation & Physical Medicine without date limitations for the following key words: laser therapy, phototherapy, fatigue, exercise, circulation, microcirculation, and photobiomodulation. Study Selection Eligible studies had to be original research published in English as full papers, involve human participants, and receive a minimum score of 7 out of 10 on the Physiotherapy Evidence Database (PEDro) scale. Data Extraction Data of interest included elapsed time to fatigue, total number of repetitions to fatigue, total work performed, maximal voluntary isometric contraction (strength), electromyographic activity, and postexercise biomarker levels. We recorded the PEDro scores, beam characteristics, and treatment variables and calculated the therapeutic outcomes and effect sizes for the data sets. Data Synthesis In total, 12 randomized controlled trials met the inclusion criteria. However, we excluded data from 2 studies, leaving 32 data sets from 10 studies. Twenty-four of the 32 data sets contained differences between active phototherapy and sham (placebo-control) treatment conditions for the various outcome measures. Exposing skeletal muscle to single-diode and multidiode laser or multidiode LED therapy was shown to positively affect physical performance by delaying the onset of fatigue, reducing the fatigue response, improving postexercise recovery, and protecting cells from exercise-induced damage. Conclusions Phototherapy administered before resistance exercise consistently has been found to provide ergogenic and prophylactic benefits to skeletal muscle.

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In Vivo Electrical Stimulation for the Assessment of Skeletal Muscle Contractile Function in Murine Models

Methods in Molecular Biology - Investigations of Early Nutrition Effects on Long-Term Health ◽

10.1007/978-1-4939-7614-0_26 ◽

2018 ◽

pp. 381-395

Author(s):

Kaio F. Vitzel ◽

Marco A. Fortes ◽

Gabriel Nasri Marzuca-Nassr ◽

Maria V. M. Scervino ◽

Carlos H. Pinheiro ◽

...

Keyword(s):

Skeletal Muscle ◽

Electrical Stimulation ◽

Contractile Function ◽

Murine Models ◽

Muscle Contractile

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Skeletal Muscle Contractile Protein Function is Preserved in Human Heart Failure.

Cardiopulmonary Physical Therapy Journal ◽

10.1097/01823246-200819030-00005 ◽

2008 ◽

Vol 19 (3) ◽

pp. 98

Author(s):

Y Okada ◽

M J Toh ◽

P. VanBuren

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Protein Function ◽

Human Heart ◽

Contractile Protein ◽

Human Heart Failure ◽

Muscle Contractile

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Dietary fish oil delays hypoxic skeletal muscle fatigue and enhances caffeine-stimulated contractile recovery in the rat in vivo hindlimb

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2016-0501 ◽

2017 ◽

Vol 42 (6) ◽

pp. 613-620 ◽

Cited By ~ 3

Author(s):

Gregory E. Peoples ◽

Peter L. McLennan

Keyword(s):

Skeletal Muscle ◽

Fish Oil ◽

Muscle Fatigue ◽

Contractile Function ◽

Physiological Role ◽

Muscle Bundle ◽

Skeletal Muscle Fatigue ◽

Dietary Fish ◽

Contractile Recovery ◽

Muscle Contractile

Oxygen efficiency influences skeletal muscle contractile function during physiological hypoxia. Dietary fish oil, providing docosahexaenoic acid (DHA), reduces the oxygen cost of muscle contraction. This study used an autologous perfused rat hindlimb model to examine the effects of a fish oil diet on skeletal muscle fatigue during an acute hypoxic challenge. Male Wistar rats were fed a diet rich in saturated fat (SF), long-chain (LC) n-6 polyunsaturated fatty acids (n-6 PUFA), or LC n-3 PUFA DHA from fish oil (FO) (8 weeks). During anaesthetised and ventilated conditions (normoxia 21% O2 (SaO2–98%) and hypoxia 14% O2 (SaO2–89%)) the hindlimb was perfused at a constant flow and the gastrocnemius–plantaris–soleus muscle bundle was stimulated via sciatic nerve (2 Hz, 6–12V, 0.05 ms) to established fatigue. Caffeine (2.5, 5, 10 mM) was supplied to the contracting muscle bundle via the arterial cannula to assess force recovery. Hypoxia, independent of diet, attenuated maximal twitch tension (normoxia: 82 ± 8; hypoxia: 41 ± 2 g·g−1 tissue w.w.). However, rats fed FO sustained higher peak twitch tension compared with the SF and n-6 PUFA groups (P < 0.05), and the time to decline to 50% of maximum twitch tension was extended (SF: 546 ± 58; n-6 PUFA: 522 ± 58; FO: 792 ± 96 s; P < 0.05). In addition, caffeine-stimulated skeletal muscle contractile recovery was enhanced in the FO-fed animals (SF: 41 ± 3; n-6 PUFA: 40 ± 4; FO: 52 ± 7% recovery; P < 0.05). These results support a physiological role of DHA in skeletal muscle membranes when exposed to low-oxygen stress that is consistent with the attenuation of muscle fatigue under physiologically normoxic conditions.

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