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Structural, Chemical and Energetic Signals in Striated Muscle Function

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 14227

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Special Issue Editors

Prof. Dr. P. Bryant Chase

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Guest Editor

Department of Biological Science, Florida State University, Tallahassee, FL 32306-4370, USA
Interests: cellular and molecular biomechanics of cardiac and skeletal muscle; non-canonical roles of troponin and tropomyosin

Dr. Jose Renato Pinto

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Guest Editor

College of Medicine, Florida State University, Tallahassee, FL 32306-4300, USA
Interests: troponin; striated muscle regulation; myocyte contractility; mechanics of striated muscle; cardiomyocyte biology; muscle biophysics and biochemistry

Prof. Dr. Kenneth A. Taylor

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Guest Editor

Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306-4380, USA
Interests: striated muscle; myosin filaments; Z-disk; muscle structure; muscle biophysics

Special Issue Information

Dear Colleagues,

Molecular signals in striated muscle underlie a wide range of physiological processes such as development and normal function of cardiac and skeletal muscles, and may participate in or even cause progressive changes in pathophysiology. Intracellular Ca²⁺—both Ca²⁺ transients that activate contraction and the Ca²⁺ level at rest—and protein phosphorylation are well-known signals that deserve further attention, along with other intracellular chemical signaling pathways. Cellular energetics signaling bridges chemical (ATP, ADP, AMP, mTOR, etc.) with thermodynamic parameters (esp. ΔG_ATP). In the body, muscle cells receive chemical signals such as those that influence metabolism, growth and repair, and the muscle itself acts as an endocrine organ by releasing chemical signals. Molecular and cellular contacts and the force generated by the muscle provide mechanical signals that parallel and accentuate the chemical and energetic signals. All of these signaling mechanisms involve a wide range of molecular structures and critical changes in those structures.

We are interested in submissions that focus on specific aspects of signaling pathways in muscle (vertebrate and invertebrate), or integrate these signaling pathways to modulate muscle structure and function in the short-term, or in the long-term through alteration of gene expression in the myocyte nucleus.

Prof. Dr. P. Bryant Chase
Dr. Jose Renato Pinto
Prof. Dr. Kenneth A. Taylor
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

striated muscle
sarcomere
thick filament
thin filament
myosin
actin
troponin
tropomyosin
calcium
ATP
ADP
cellular signaling
endocrine

Published Papers (7 papers)

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Research

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31 pages, 3457 KiB

Open AccessArticle

Creatine Kinase Equilibration and ΔG_ATP over an Extended Range of Physiological Conditions: Implications for Cellular Energetics, Signaling, and Muscle Performance

by Robert Woodbury Wiseman, Caleb Micah Brown, Thomas Wesley Beck, Jeffrey John Brault, Tyler Robert Reinoso, Yun Shi and Prescott Bryant Chase

Int. J. Mol. Sci. 2023, 24(17), 13244; https://doi.org/10.3390/ijms241713244 - 26 Aug 2023

Cited by 2 | Viewed by 1154

Abstract

In this report, we establish a straightforward method for estimating the equilibrium constant for the creatine kinase reaction (CK K_eq″) over wide but physiologically and experimentally relevant ranges of pH, Mg²⁺ and temperature. Our empirical formula for CK K_eq″ is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we were able to obtain improved estimates of ΔG_ATP, necessitating the reinvestigation of previously reported ADP- and ΔG_ATP-dependent processes. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies and pH is not altered, the maximum Ca²⁺-activated isometric force depends on ΔG_ATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis around the role of submicromolar ADP in force generation. Full article

(This article belongs to the Special Issue Structural, Chemical and Energetic Signals in Striated Muscle Function)

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14 pages, 4134 KiB

Open AccessArticle

Phosphorylation of AMPKα at Ser485/491 Is Dependent on Muscle Contraction and Not Muscle-Specific IGF-I Overexpression

by Chih-Hsuan Chou and Elisabeth R. Barton

Int. J. Mol. Sci. 2023, 24(15), 11950; https://doi.org/10.3390/ijms241511950 - 26 Jul 2023

Cited by 1 | Viewed by 816

Abstract

Glucose is an important fuel for highly active skeletal muscles. Increased adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratios during repetitive contractions trigger AMP-activated protein kinase (AMPK), indicated by phosphorylation of AMPKα^Thr172, which promotes glucose uptake to support heightened energy needs, but it also suppresses anabolic processes. Inhibition of AMPK can occur by protein kinase B (AKT)-mediated phosphorylation of AMPKα^Ser485/491, releasing its brake on growth. The influence of insulin-like growth factor I (IGF-I) on glucose uptake and its interplay with AMPK activation is not well understood. Thus, the goal of this study was to determine if increased muscle IGF-I altered AMPKα phosphorylation and activity during muscle contraction. Adult male mice harboring the rat Igf1a cDNA regulated by the fast myosin light chain promoter (mIgf1^+/+) and wildtype littermates (WT) were used in the study. mIgf1^+/+ mice had enhanced glucose tolerance and insulin-stimulated glucose uptake, but similar exercise capacity. Fatiguing stimulations of extensor digitorum longus (EDL) muscles resulted in upregulated AMPKα phosphorylation at both Thr172 and Ser485/491 in WT and mIgf1^+/+ muscles. No differences in the phosphorylation response of the downstream AMPK target TBC1D1 were observed, but phosphorylation of raptor was significantly higher only in WT muscles. Further, total raptor content was elevated in mIgf1^+/+ muscles. The results show that high muscle IGF-I can enhance glucose uptake under resting conditions; however, in contracting muscle, it is not sufficient to inhibit AMPK activity. Full article

(This article belongs to the Special Issue Structural, Chemical and Energetic Signals in Striated Muscle Function)

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15 pages, 2368 KiB

Open AccessArticle

Sarcospan Deficiency Increases Oxidative Stress and Arrhythmias in Hearts after Acute Ischemia-Reperfusion Injury

by Hyun Seok Hwang, Aida Rahimi Kahmini, Julia Prascak, Alexis Cejas-Carbonell, Isela C. Valera, Samantha Champion, Mikayla Corrigan, Florence Mumbi and Michelle S. Parvatiyar

Int. J. Mol. Sci. 2023, 24(14), 11868; https://doi.org/10.3390/ijms241411868 - 24 Jul 2023

Viewed by 1436

Abstract

The protein sarcospan (SSPN) is an integral member of the dystrophin-glycoprotein complex (DGC) and has been shown to be important in the heart during the development and the response to acute stress. In this study, we investigated the role of SSPN in the cardiac response to acute ischemia-reperfusion (IR) injury in SSPN-deficient (SSPN^−/−) mice. First, the hemodynamic response of SSPN^−/− mice was tested and was similar to SSPN^+/+ (wild-type) mice after isoproterenol injection. Using the in situ Langendorff perfusion method, SSPN^−/− hearts were subjected to IR injury and found to have increased infarct size and arrhythmia susceptibility compared to SSPN^+/+. Ca²⁺ handling was assessed in single cardiomyocytes and diastolic Ca²⁺ levels were increased after acute β-AR stimulation in SSPN^+/+ but not SSPN^−/−. It was also found that SSPN^−/− cardiomyocytes had reduced Ca²⁺ SR content compared to SSPN^+/+ but similar SR Ca²⁺ release. Next, we used qRT-PCR to examine gene expression of Ca²⁺ handling proteins after acute IR injury. SSPN^−/− hearts showed a significant decrease in L-type Ca²⁺ channels and a significant increase in Ca²⁺ release channel (RyR2) expression. Interestingly, under oxidizing conditions reminiscent of IR, SSPN^−/− cardiomyocytes, had increased H₂O₂-induced reactive oxygen species production compared to SSPN^+/+. Examination of oxidative stress proteins indicated that NADPH oxidase 4 and oxidized CAMKII were increased in SSPN^−/− hearts after acute IR injury. These results suggest that increased arrhythmia susceptibility in SSPN^−/− hearts post-IR injury may arise from alterations in Ca²⁺ handling and a reduced capacity to regulate oxidative stress pathways. Full article

(This article belongs to the Special Issue Structural, Chemical and Energetic Signals in Striated Muscle Function)

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25 pages, 3385 KiB

Open AccessArticle

Structure of the Flight Muscle Thick Filament from the Bumble Bee, Bombus ignitus, at 6 Å Resolution

by Jiawei Li, Hamidreza Rahmani, Fatemeh Abbasi Yeganeh, Hosna Rastegarpouyani, Dianne W. Taylor, Neil B. Wood, Michael J. Previs, Hiroyuki Iwamoto and Kenneth A. Taylor

Int. J. Mol. Sci. 2023, 24(1), 377; https://doi.org/10.3390/ijms24010377 - 26 Dec 2022

Cited by 5 | Viewed by 1824

Abstract

Four insect orders have flight muscles that are both asynchronous and indirect; they are asynchronous in that the wingbeat frequency is decoupled from the frequency of nervous stimulation and indirect in that the muscles attach to the thoracic exoskeleton instead of directly to the wing. Flight muscle thick filaments from two orders, Hemiptera and Diptera, have been imaged at a subnanometer resolution, both of which revealed a myosin tail arrangement referred to as “curved molecular crystalline layers”. Here, we report a thick filament structure from the indirect flight muscles of a third insect order, Hymenoptera, the Asian bumble bee Bombus ignitus. The myosin tails are in general agreement with previous determinations from Lethocerus indicus and Drosophila melanogaster. The Skip 2 region has the same unusual structure as found in Lethocerus indicus thick filaments, an α-helix discontinuity is also seen at Skip 4, but the orientation of the Skip 1 region on the surface of the backbone is less angled with respect to the filament axis than in the other two species. The heads are disordered as in Drosophila, but we observe no non-myosin proteins on the backbone surface that might prohibit the ordering of myosin heads onto the thick filament backbone. There are strong structural similarities among the three species in their non-myosin proteins within the backbone that suggest how one previously unassigned density in Lethocerus might be assigned. Overall, the structure conforms to the previously observed pattern of high similarity in the myosin tail arrangement, but differences in the non-myosin proteins. Full article

(This article belongs to the Special Issue Structural, Chemical and Energetic Signals in Striated Muscle Function)

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14 pages, 2990 KiB

Open AccessArticle

MgADP Promotes Myosin Head Movement toward Actin at Low [Ca²⁺] to Increase Force Production and Ca²⁺-Sensitivity of Contraction in Permeabilized Porcine Myocardial Strips

by Peter O. Awinda, Weikang Ma, Kyrah L. Turner, Jing Zhao, Henry Gong, Mindy S. Thompson, Kenneth S. Campbell, Thomas C. Irving and Bertrand C. W. Tanner

Int. J. Mol. Sci. 2022, 23(23), 15084; https://doi.org/10.3390/ijms232315084 - 1 Dec 2022

Cited by 3 | Viewed by 1475

Abstract

Myosin cross-bridges dissociate from actin following Mg²⁺-adenosine triphosphate (MgATP) binding. Myosin hydrolyses MgATP into inorganic phosphate (P_i) and Mg²⁺-adenosine diphosphate (ADP), and release of these hydrolysis products drives chemo-mechanical energy transitions within the cross-bridge cycle to power muscle contraction. Some forms of heart disease are associated with metabolic or enzymatic dysregulation of the MgATP-MgADP nucleotide pool, resulting in elevated cytosolic [MgADP] and impaired muscle relaxation. We investigated the mechanical and structural effects of increasing [MgADP] in permeabilized myocardial strips from porcine left ventricle samples. Sarcomere length was set to 2.0 µm at 28 °C, and all solutions contained 3% dextran T-500 to compress myofilament lattice spacing to near-physiological values. Under relaxing low [Ca²⁺] conditions (pCa 8.0, where pCa = −log₁₀[Ca²⁺]), tension increased as [MgADP] increased from 0-5 mM. Complementary small-angle X-ray diffraction measurements show that the equatorial intensity ratio, I_1,1/I_1,0, also increased as [MgADP] increased from 0 to 5 mM, indicating myosin head movement away from the thick-filament backbone towards the thin-filament. Ca²⁺-activated force-pCa measurements show that Ca²⁺-sensitivity of contraction increased with 5 mM MgADP, compared to 0 mM MgADP. These data show that MgADP augments tension at low [Ca²⁺] and Ca²⁺-sensitivity of contraction, suggesting that MgADP destabilizes the quasi-helically ordered myosin OFF state, thereby shifting the cross-bridge population towards the disordered myosin ON state. Together, these results indicate that MgADP enhances the probability of cross-bridge binding to actin due to enhancement of both thick and thin filament-based activation mechanisms. Full article

(This article belongs to the Special Issue Structural, Chemical and Energetic Signals in Striated Muscle Function)

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Review

Jump to: Research

24 pages, 1200 KiB

Open AccessReview

Cardiac Sarcomere Signaling in Health and Disease

by Ashley A. Martin, Brian R. Thompson, Dongwoo Hahn, Addeli Bez Batti Angulski, Nora Hosny, Houda Cohen and Joseph M. Metzger

Int. J. Mol. Sci. 2022, 23(24), 16223; https://doi.org/10.3390/ijms232416223 - 19 Dec 2022

Cited by 4 | Viewed by 4005

Abstract

The cardiac sarcomere is a triumph of biological evolution wherein myriad contractile and regulatory proteins assemble into a quasi-crystalline lattice to serve as the central point upon which cardiac muscle contraction occurs. This review focuses on the many signaling components and mechanisms of regulation that impact cardiac sarcomere function. We highlight the roles of the thick and thin filament, both as necessary structural and regulatory building blocks of the sarcomere as well as targets of functionally impactful modifications. Currently, a new focus emerging in the field is inter-myofilament signaling, and we discuss here the important mediators of this mechanism, including myosin-binding protein C and titin. As the understanding of sarcomere signaling advances, so do the methods with which it is studied. This is reviewed here through discussion of recent live muscle systems in which the sarcomere can be studied under intact, physiologically relevant conditions. Full article

(This article belongs to the Special Issue Structural, Chemical and Energetic Signals in Striated Muscle Function)

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16 pages, 1038 KiB

Open AccessReview

Arrhythmogenic Cardiomyopathy: Exercise Pitfalls, Role of Connexin-43, and Moving beyond Antiarrhythmics

by Isabella Leite Coscarella, Maicon Landim-Vieira, José Renato Pinto and Stephen P. Chelko

Int. J. Mol. Sci. 2022, 23(15), 8753; https://doi.org/10.3390/ijms23158753 - 6 Aug 2022

Cited by 6 | Viewed by 2530

Abstract

Arrhythmogenic Cardiomyopathy (ACM), a Mendelian disorder that can affect both left and right ventricles, is most often associated with pathogenic desmosomal variants that can lead to fibrofatty replacement of the myocardium, a pathological hallmark of this disease. Current therapies are aimed to prevent the worsening of disease phenotypes and sudden cardiac death (SCD). Despite the use of implantable cardioverter defibrillators (ICDs) there is no present therapy that would mitigate the loss in electrical signal and propagation by these fibrofatty barriers. Recent studies have shown the influence of forced vs. voluntary exercise in a variety of healthy and diseased mice; more specifically, that exercised mice show increased Connexin-43 (Cx43) expression levels. Fascinatingly, increased Cx43 expression ameliorated the abnormal electrical signal conduction in the myocardium of diseased mice. These findings point to a major translational pitfall in current therapeutics for ACM patients, who are advised to completely cease exercising and already demonstrate reduced Cx43 levels at the myocyte intercalated disc. Considering cardiac dysfunction in ACM arises from the loss of cardiomyocytes and electrical signal conduction abnormalities, an increase in Cx43 expression—promoted by low to moderate intensity exercise and/or gene therapy—could very well improve cardiac function in ACM patients. Full article

(This article belongs to the Special Issue Structural, Chemical and Energetic Signals in Striated Muscle Function)

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