Sequential effects of GSNO and H2O2 on the Ca2+ sensitivity of the contractile apparatus of fast- and slow-twitch skeletal muscle fibers from the rat

Reactive oxygen species (ROS), such as hydrogen peroxide (H2O2) and nitric oxide (NO), have been shown to differentially alter the Ca2+ sensitivity of the contractile apparatus of fast-twitch skeletal muscle, leading to the proposal that normal muscle function is controlled by perturbations in the amounts of these two groups of molecules ( 28 ). However, no previous studies have examined whether these opposing actions are retained when the contractile apparatus is subjected to both molecule types. Using mechanically skinned fast- and slow-twitch skeletal muscle fibers of the rat, we compared the effects of sequential addition of nitrosoglutathione (GSNO), a NO donor, and H2O2 on the Ca2+ sensitivity of the contractile apparatus. As expected from previous reports in fast-twitch fibers, when added separately, GSNO (1 mM) reduced the Ca2+ sensitivity of the contractile apparatus, whereas H2O2 (10 mM; added during contractions) increased the Ca2+ sensitivity of the contractile apparatus. When added sequentially to the same fiber, such that the oxidation by one molecule (e.g., GSNO) preceded the oxidation by the other (e.g., H2O2), and vice versa, the individual effects of both molecules on the Ca2+ sensitivity were retained. Interestingly, neither molecule had any effect on the Ca2+ sensitivity of slow-twitch skeletal muscle. The data show that H2O2 and GSNO retain the capacity to independently affect the contractile apparatus to modulate force. Furthermore, the absence of effects in slow-twitch muscle may further explain why this fiber type is relatively insensitive to fatigue.

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Activity-dependent nuclear translocation and intranuclear distribution of NFATc in adult skeletal muscle fibers

The Journal of Cell Biology ◽

10.1083/jcb.200103020 ◽

2001 ◽

Vol 155 (1) ◽

pp. 27-40 ◽

Cited By ~ 130

Author(s):

Yewei Liu ◽

Zoltán Cseresnyés ◽

William R. Randall ◽

Martin F. Schneider

Keyword(s):

Skeletal Muscle ◽

Electrical Stimulation ◽

Nuclear Translocation ◽

Fiber Type ◽

Muscle Fibers ◽

Adult Skeletal Muscle ◽

Skeletal Muscle Fibers ◽

Slow Twitch ◽

Nuclear Foci ◽

Fast Twitch

TTranscription factor nuclear factor of activated T cells NFATc (NFATc1, NFAT2) may contribute to slow-twitch skeletal muscle fiber type–specific gene expression. Green fluorescence protein (GFP) or FLAG fusion proteins of either wild-type or constitutively active mutant NFATc [NFATc(S→A)] were expressed in cultured adult mouse skeletal muscle fibers from flexor digitorum brevis (predominantly fast-twitch). Unstimulated fibers expressing NFATc(S→A) exhibited a distinct intranuclear pattern of NFATc foci. In unstimulated fibers expressing NFATc–GFP, fluorescence was localized at the sarcomeric z-lines and absent from nuclei. Electrical stimulation using activity patterns typical of slow-twitch muscle, either continuously at 10 Hz or in 5-s trains at 10 Hz every 50 s, caused cyclosporin A–sensitive appearance of fluorescent foci of NFATc–GFP in all nuclei. Fluorescence of nuclear foci increased during the first hour of stimulation and then remained constant during a second hour of stimulation. Kinase inhibitors and ionomycin caused appearance of nuclear foci of NFATc–GFP without electrical stimulation. Nuclear translocation of NFATc–GFP did not occur with either continuous 1 Hz stimulation or with the fast-twitch fiber activity pattern of 0.1-s trains at 50 Hz every 50 s. The stimulation pattern–dependent nuclear translocation of NFATc demonstrated here could thus contribute to fast-twitch to slow-twitch fiber type transformation.

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Na current density at and away from end plates on rat fast- and slow-twitch skeletal muscle fibers

AJP Cell Physiology ◽

10.1152/ajpcell.1992.262.1.c229 ◽

1992 ◽

Vol 262 (1) ◽

pp. C229-C234 ◽

Cited By ~ 67

Author(s):

R. L. Ruff

Keyword(s):

Skeletal Muscle ◽

Current Density ◽

Muscle Fibers ◽

Postsynaptic Membrane ◽

Na Current ◽

End Plate ◽

Skeletal Muscle Fibers ◽

Slow Twitch ◽

Slow Twitch Fibers ◽

Fast Twitch

Na current density and membrane capacitance were studied with the loose patch voltage clamp technique on rat fast- and slow-twitch skeletal muscle fibers at three different regions on the fibers: 1) the end plate border, 2) greater than 200 microns from the end plate (extrajunctional), and 3) on the end plate postsynaptic membrane. Fibers were treated with collagenase to improve visualization of the end plate and to enzymatically remove the nerve terminal. The capacitance of membrane patches was similar on fast- and slow-twitch fibers and patches of membrane on the end plate had twice the capacitance of patches elsewhere. For fast- and slow-twitch fibers, the sizes of the Na current normalized to the area of the patch were as follows: end plate greater than end plate border greater than extrajunctional. For both types of fibers, the amplitudes of the Na current normalized to the capacitance of the membrane patch were as follows: end plate approximately end plate border greater than extrajunctional. At each of the three regions, the Na current densities were larger on fast-twitch fibers and fast-twitch fibers had a larger increase in Na current density at the end plate border compared with extrajunctional membrane.

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Myofibrillar regulatory mechanisms of stretch activation in mammalian striated muscle

10.32469/10355/63384 ◽

2017 ◽

Author(s):

◽

Joel C. Robinett

Keyword(s):

Skeletal Muscle ◽

Striated Muscle ◽

Muscle Fibers ◽

Stretch Activation ◽

Skeletal Muscle Fibers ◽

Slow Twitch ◽

Low Levels ◽

Slow Twitch Fibers ◽

Fast Twitch ◽

Transient Force

Stretch activation is described as a delayed increase in force after an imposed stretch. This process is essential in the flight muscles of many insects and is also observed, to some degree, in mammalian striated muscles. The mechanistic basis for stretch activation remains uncertain, although it appears to involve cooperative activation of the thin filaments (12, 80). The purpose of this study was to address myofibrillar regulatory mechanisms of stretch activation in mammalian striated muscle. For these studies, permeabilized rat slow-twitch and fast-twitch skeletal muscle fibers were mounted between a force transducer and motor, and a slack-re-stretch maneuver was performed over a range of Ca[superscript 2+] activation levels. Following slack-re-stretch there was a stretch activation process that often resulted in a transient force overshoot (P[subscript TO]), which was quantified relative to steady-state isometric force. P[subscript TO] was highly dependent upon Ca[superscript 2+] activation level, and the relative magnitude of P[subscript TO] was greater in slow-twitch fibers than fast-twitch fibers. In both slow-twitch and fast-twitch fibers, force redevelopment involved a fast, Ca[superscript 2+] activation dependent process (k1) and a slower, less activation dependent process (k2). Interestingly, the two processes converged at low levels of Ca[superscript 2+] activation in both fiber types. P[subscript TO] also contained a relaxation phase, which progressively slowed as Ca[superscript 2+] activation levels increased and was more Ca[superscript 2+] activation dependent in slow-twitch fibers. These results suggest that stretch activation may not be solely regulated by the extent of apparent cooperative activation of force due to a higher relative level of stretch activation in the less cooperative slow-twitch skeletal muscle fiber. Next, we investigated an additional potential molecular mechanism by regulating stretch activation in mammalian striated muscle. Along these lines, our lab has previously observed that PKA-induced phosphorylation of cMyBP-C and cTnI elicited a significant increase in transient force overshoot following slack-re-stretch maneuver in permeabilized cardiac myocytes (29). Interestingly, in slow-twitch skeletal muscle fibers MyBP-C but not ssTnI is phosphorylated by PKA (28). We, thus, took advantage of this variation in substrates phosphorylated by PKA to investigate the effects of PKA-induced phosphorylation of MyBP-C on stretch activation in slow-twitch skeletal muscle fibers. Following PKA treatment of skinned slow-twitch skeletal muscle fibers, the magnitude of P[subscript TO] more than doubled, but this only occurred at low levels of Ca[superscript 2+] activation (i.e., [approximately]25% maximal Ca[superscript 2+] activated force). Also, force redevelopment rates were significantly increased over the entire range of Ca[superscript 2+] activation levels following PKA treatment. In a similar manner, force decay rates showed a tendency of being faster following PKA treatment, however, were only statistically significantly faster at 50% Ca[superscript 2+] activation. Overall, these results are consistent with a model whereby stretch transiently increases the number of cross-bridges made available for force generation and PKA phosphorylation of MyBP-C enhances these stretch activation processes.

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Comparison of the effects of inorganic phosphate on caffeine-induced Ca2+ release in fast- and slow-twitch mammalian skeletal muscle

AJP Cell Physiology ◽

10.1152/ajpcell.00155.2007 ◽

2008 ◽

Vol 294 (1) ◽

pp. C97-C105 ◽

Cited By ~ 7

Author(s):

Giuseppe S. Posterino ◽

Stacey L. Dunn

Keyword(s):

Skeletal Muscle ◽

Sarcoplasmic Reticulum ◽

Inorganic Phosphate ◽

Fiber Type ◽

Muscle Fibers ◽

Creatine Phosphate ◽

Mammalian Skeletal Muscle ◽

Time Integral ◽

Slow Twitch ◽

Fast Twitch

We compared the effects of 50 mM Pi on caffeine-induced Ca2+ release in mechanically skinned fast-twitch (FT) and slow-twitch (ST) skeletal muscle fibers of the rat. The time integral (area) of the caffeine response was reduced by ∼57% (FT) and ∼27% (ST) after 30 s of exposure to 50 mM Pi in either the presence or absence of creatine phosphate (to buffer ADP). Differences in the sarcoplasmic reticulum (SR) Ca2+ content between FT and ST fibers [∼40% vs. 100% SR Ca2+ content (pCa 6.7), respectively] did not contribute to the different effects of Pi observed; underloading the SR of ST fibers so that the SR Ca2+ content approximated that of FT fibers resulted in an even smaller (∼21%), but not significant, reduction in caffeine-induced Ca2+ release by Pi. These observed differences between FT and ST fibers could arise from fiber-type differences in the ability of the SR to accumulate Ca2+-Pi precipitate. To test this, fibers were Ca2+ loaded in the presence of 50 mM Pi. In FT fibers, the maximum SR Ca2+ content (pCa 6.7) was subsequently increased by up to 13 times of that achieved when loading for 2 min in the absence of Pi. In ST fibers, the SR Ca2+ content was only doubled. These data show that Ca2+ release in ST fibers was less affected by Pi than FT fibers, and this may be due to a reduced capacity of ST SR to accumulate Ca2+-Pi precipitate. This may account, in part, for the fatigue-resistant nature of ST fibers.

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Six1 and Eya1 Expression Can Reprogram Adult Muscle from the Slow-Twitch Phenotype into the Fast-Twitch Phenotype

Molecular and Cellular Biology ◽

10.1128/mcb.24.14.6253-6267.2004 ◽

2004 ◽

Vol 24 (14) ◽

pp. 6253-6267 ◽

Cited By ~ 132

Author(s):

Raphaelle Grifone ◽

Christine Laclef ◽

François Spitz ◽

Soledad Lopez ◽

Josiane Demignon ◽

...

Keyword(s):

Skeletal Muscle ◽

Fiber Type ◽

Muscle Fibers ◽

Slow Twitch Muscle ◽

Slow Twitch ◽

Metabolic Properties ◽

Transcriptional Complex ◽

High Level ◽

Fast Twitch ◽

Aldolase A

ABSTRACT Muscle fibers show great differences in their contractile and metabolic properties. This diversity enables skeletal muscles to fulfill and adapt to different tasks. In this report, we show that the Six/Eya pathway is implicated in the establishment and maintenance of the fast-twitch skeletal muscle phenotype. We demonstrate that the MEF3/Six DNA binding element present in the aldolase A pM promoter mediates the high level of activation of this promoter in fast-twitch glycolytic (but not in slow-twitch) muscle fibers. We also show that among the Six and Eya gene products expressed in mouse skeletal muscle, Six1 and Eya1 proteins accumulate preferentially in the nuclei of fast-twitch muscles. The forced expression of Six1 and Eya1 together in the slow-twitch soleus muscle induced a fiber-type transition characterized by the replacement of myosin heavy chain I and IIA isoforms by the faster IIB and/or IIX isoforms, the activation of fast-twitch fiber-specific genes, and a switch toward glycolytic metabolism. Collectively, these data identify Six1 and Eya1 as the first transcriptional complex that is able to reprogram adult slow-twitch oxidative fibers toward a fast-twitch glycolytic phenotype.

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The KATP channel Kir6.2 subunit content is higher in glycolytic than oxidative skeletal muscle fibers

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00663.2010 ◽

2011 ◽

Vol 301 (4) ◽

pp. R916-R925 ◽

Cited By ~ 18

Author(s):

Krystyna Banas ◽

Charlene Clow ◽

Bernard J. Jasmin ◽

Jean-Marc Renaud

Keyword(s):

Skeletal Muscle ◽

Cross Sections ◽

Fiber Type ◽

Energy Levels ◽

Muscle Fibers ◽

Metabolic Stress ◽

Oxidative Capacity ◽

Fiber Types ◽

Fiber Damage ◽

The Individual

It has long been suggested that in skeletal muscle, the ATP-sensitive K+ channel (KATP) channel is important in protecting energy levels and that abolishing its activity causes fiber damage and severely impairs function. The responses to a lack of KATP channel activity vary between muscles and fibers, with the severity of the impairment being the highest in the most glycolytic muscle fibers. Furthermore, glycolytic muscle fibers are also expected to face metabolic stress more often than oxidative ones. The objective of this study was to determine whether the t-tubular KATP channel content differs between muscles and fiber types. KATP channel content was estimated using a semiquantitative immunofluorescence approach by staining cross sections from soleus, extensor digitorum longus (EDL), and flexor digitorum brevis (FDB) muscles with anti-Kir6.2 antibody. Fiber types were determined using serial cross sections stained with specific antimyosin I, IIA, IIB, and IIX antibodies. Changes in Kir6.2 content were compared with changes in CaV1.1 content, as this Ca2+ channel is responsible for triggering Ca2+ release from sarcoplasmic reticulum. The Kir6.2 content was the lowest in the oxidative soleus and the highest in the glycolytic EDL and FDB. At the individual fiber level, the Kir6.2 content within a muscle was in the order of type IIB > IIX > IIA ≥ I. Interestingly, the Kir6.2 content for a given fiber type was significantly different between soleus, EDL, and FDB, and highest in FDB. Correlations of relative fluorescence intensities from the Kir6.2 and CaV1.1 antibodies were significant for all three muscles. However, the variability in content between the three muscles or individual fibers was much greater for Kir6.2 than for CaV1.1. It is suggested that the t-tubular KATP channel content increases as the glycolytic capacity increases and as the oxidative capacity decreases and that the expression of KATP channels may be linked to how often muscles/fibers face metabolic stress.

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The Adaptive Potential of Skeletal Muscle Fibers

Canadian Journal of Applied Physiology ◽

10.1139/h02-023 ◽

2002 ◽

Vol 27 (4) ◽

pp. 423-448 ◽

Cited By ~ 109

Author(s):

Dirk Pette

Keyword(s):

Skeletal Muscle ◽

Fiber Type ◽

Muscle Fibers ◽

Protein Isoforms ◽

Mammalian Skeletal Muscle ◽

Adaptive Potential ◽

Hybrid Fibers ◽

Neuromuscular Activity ◽

Skeletal Muscle Fibers ◽

Initial Location

Mammalian skeletal muscle fibers display a great adaptive potential. This potential results from the ability of muscle fibers to adjust their molecular, functional, and metabolic properties in response to altered functional demands, such as changes in neuromuscular activity or mechanical loading. Adaptive changes in the expression of myofibrillar and other protein isoforms result in fiber type transitions. These transitions occur in a sequential order and encompass a spectrum of pure and hybrid fibers. Depending on the quality, intensity, and duration of the alterations in functional demand, muscle fibers may undergo functional transitions in the direction of slow or fast, as well as metabolic transitions in the direction of aerobic-oxidative or glycotytic. The maximum range of possible transitions in either direction depends on the fiber phenotype and is determined by its initial location in the fiber spectrum. Key words: Ca-sequestering proteins, energy metabolism, fiber type transition, myofibrillar protein isofonns, myosin, neuromuscular activity

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Phenotypic Modulation of Skeletal Muscle Fibers in LPIN1-Deficient Lipodystrophic (fld) Mice

Veterinary Pathology ◽

10.1177/0300985818809126 ◽

2018 ◽

Vol 56 (2) ◽

pp. 322-331

Author(s):

Rani S. Sellers ◽

S. Radma Mahmood ◽

Geoffrey S. Perumal ◽

Frank P. Macaluso ◽

Irwin J. Kurland

Keyword(s):

Electron Microscopy ◽

Skeletal Muscle ◽

Fiber Type ◽

Periodic Acid ◽

Muscle Fibers ◽

Myosin Atpase ◽

Hybrid Fibers ◽

Periodic Acid Schiff ◽

Skeletal Muscle Fibers ◽

Lipin 1

Lipin-1 ( Lpin1)–deficient lipodystrophic mice have scant and immature adipocytes and develop transient fatty liver early in life. Unlike normal mice, these mice cannot rely on stored triglycerides to generate adenosine triphosphate (ATP) from the β-oxidation of fatty acids during periods of fasting. To compensate, these mice store much higher amounts of glycogen in skeletal muscle and liver than wild-type mice in order to support energy needs during periods of fasting. Our studies demonstrated that there are phenotypic changes in skeletal muscle fibers that reflect an adaptation to this unique metabolic situation. The phenotype of skeletal muscle (soleus, gastrocnemius, plantaris, and extensor digitorum longus [EDL]) from Lpin1-/- was evaluated using various methods including immunohistochemistry for myosin heavy chains (Myh) 1, 2, 2a, 2b, and 2x; enzyme histochemistry for myosin ATPase, cytochrome-c oxidase (COX), and succinyl dehydrogenase (SDH); periodic acid–Schiff; and transmission electron microscopy. Fiber-type changes in the soleus muscle of Lpin1-/- mice were prominent and included decreased Myh1 expression with concomitant increases in Myh2 expression and myosin-ATPase activity; this change was associated with an increase in the presence of Myh1/2a or Myh1/2x hybrid fibers. Alterations in mitochondrial enzyme activity (COX and SDH) were apparent in the myofibers in the soleus, gastrocnemius, plantaris, and EDL muscles. Electron microscopy revealed increases in the subsarcolemmal mitochondrial mass in the muscles of Lpin1-/- mice. These data demonstrate that lipin-1 deficiency results in phenotypic fiber-specific modulation of skeletal muscle necessary for compensatory fuel utilization adaptations in lipodystrophy.

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lncRNA-Six1 Is a Target of miR-1611 that Functions as a ceRNA to Regulate Six1 Protein Expression and Fiber Type Switching in Chicken Myogenesis

Cells ◽

10.3390/cells7120243 ◽

2018 ◽

Vol 7 (12) ◽

pp. 243 ◽

Cited By ~ 10

Author(s):

Manting Ma ◽

Bolin Cai ◽

Liang Jiang ◽

Bahareldin Ali Abdalla ◽

Zhenhui Li ◽

...

Keyword(s):

Fiber Type ◽

Muscle Fibers ◽

Muscle Fiber Types ◽

Fiber Types ◽

Proliferation And Differentiation ◽

Slow Twitch Muscle ◽

Fast Twitch Muscle ◽

Slow Twitch ◽

Slow Twitch Fibers ◽

Fast Twitch

Emerging studies indicate important roles for non-coding RNAs (ncRNAs) as essential regulators in myogenesis, but relatively less is known about their function. In our previous study, we found that lncRNA-Six1 can regulate Six1 in cis to participate in myogenesis. Here, we studied a microRNA (miRNA) that is specifically expressed in chickens (miR-1611). Interestingly, miR-1611 was found to contain potential binding sites for both lncRNA-Six1 and Six1, and it can interact with lncRNA-Six1 to regulate Six1 expression. Overexpression of miR-1611 represses the proliferation and differentiation of myoblasts. Moreover, miR-1611 is highly expressed in slow-twitch fibers, and it drives the transformation of fast-twitch muscle fibers to slow-twitch muscle fibers. Together, these data demonstrate that miR-1611 can mediate the regulation of Six1 by lncRNA-Six1, thereby affecting proliferation and differentiation of myoblasts and transformation of muscle fiber types.

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