scholarly journals A myosin-based mechanism for stretch activation and its possible role revealed by varying phosphate concentration in fast and slow mouse skeletal muscle fibers

2019 ◽  
Vol 317 (6) ◽  
pp. C1143-C1152 ◽  
Author(s):  
Chad R. Straight ◽  
Kaylyn M. Bell ◽  
Jared N. Slosberg ◽  
Mark S. Miller ◽  
Douglas M. Swank
Keyword(s):  
Skeletal Muscle ◽  
Isometric Force ◽  
Muscle Fibers ◽  
Muscle Length ◽  
Power Stroke ◽  
Mammalian Skeletal Muscle ◽  
Stretch Activation ◽  
Force Ratio ◽  
Slow Twitch ◽  
Fast Twitch

Stretch activation (SA) is a delayed increase in force following a rapid muscle length increase. SA is best known for its role in asynchronous insect flight muscle, where it has replaced calcium’s typical role of modulating muscle force levels during a contraction cycle. SA also occurs in mammalian skeletal muscle but has previously been thought to be too low in magnitude, relative to calcium-activated (CA) force, to be a significant contributor to force generation during locomotion. To test this supposition, we compared SA and CA force at different Pi concentrations (0–16 mM) in skinned mouse soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscle fibers. CA isometric force decreased similarly in both muscles with increasing Pi, as expected. SA force decreased with Pi in EDL (40%), leaving the SA to CA force ratio relatively constant across Pi concentrations (17–25%). In contrast, SA force increased in soleus (42%), causing a quadrupling of the SA to CA force ratio, from 11% at 0 mM Pi to 43% at 16 mM Pi, showing that SA is a significant force modulator in slow-twitch mammalian fibers. This modulation would be most prominent during prolonged muscle use, which increases Pi concentration and impairs calcium cycling. Based upon our previous Drosophila myosin isoform studies and this work, we propose that in slow-twitch fibers a rapid stretch in the presence of Pi reverses myosin’s power stroke, enabling quick rebinding to actin and enhanced force production, while in fast-twitch fibers, stretch and Pi cause myosin to detach from actin.

scholarly journals Myofibrillar regulatory mechanisms of stretch activation in mammalian striated muscle

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.

Acidosis has no effect on the ATP cost of contraction in cat fast- and slow-twitch skeletal muscles

1997 ◽  
Vol 272 (2) ◽  
pp. C485-C490 ◽  
Author(s):  
S. J. Harkema ◽  
G. R. Adams ◽  
R. A. Meyer
Keyword(s):  
Skeletal Muscle ◽  
Ex Vivo ◽  
Isometric Force ◽  
Mammalian Skeletal Muscle ◽  
Time Integral ◽  
Nuclear Magnetic Resonance Spectra ◽  
Before And After ◽  
Muscle Types ◽  
Slow Twitch ◽  
Fast Twitch

Studies of skinned fibers suggest that the rate of ATP turnover in skeletal muscle is depressed by acidosis. To examine whether this occurs in intact muscles, the ATP cost of isometric contractions was measured in ex vivo, arterially perfused cat biceps (predominantly fast-twitch) and soleus (slow-twitch) muscles under normocapnic (5% CO2) and hypercapnic (70% CO2) conditions. Hypercapnia decreased extracellular pH from 7.4 to 6.7 and intracellular pH from 7.1 to 6.5 (soleus) or 6.6 (biceps) but had no significant effect on the phosphocreatine (PCr)-to-ATP ratio in muscles at rest. The ATP cost of contraction was estimated from PCr changes, measured by gating the acquisition of 31P-nuclear magnetic resonance spectra to times before and after brief tetani (1 s at 100 Hz and 2 s at 25 Hz for biceps and soleus, respectively) or 10-s trains of twitches (2 and 1 Hz, respectively). Peak isometric force and the ATP cost of tetanic contraction (PCr/force x time integral) were not significantly different under hypercapnic compared with normocapnic conditions in either muscle (mean: 7.97 and 2.44 micromol x kg(-1) x s(-1) for biceps and soleus, respectively). Twitch force and the ATP cost per twitch decreased by nearly 50% during hypercapnic perfusion in both muscle types. The results indicate that hypercapnic acidosis has no significant effect on the ATPase rate per active myosin head in intact mammalian skeletal muscle.

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

2008 ◽  
Vol 294 (1) ◽  
pp. C97-C105 ◽  
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.

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

1992 ◽  
Vol 262 (1) ◽  
pp. C229-C234 ◽  
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.

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

2001 ◽  
Vol 155 (1) ◽  
pp. 27-40 ◽  
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.

scholarly journals Localization of sarcoplasmic reticulum proteins in rat skeletal muscle by immunofluorescence.

1979 ◽  
Vol 80 (2) ◽  
pp. 372-384 ◽  
Author(s):  
A O Jorgensen ◽  
V Kalnins ◽  
D H MacLennan
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Immunofluorescent Staining ◽  
Mammalian Skeletal Muscle ◽  
Rat Skeletal Muscle ◽  
Ultrastructural Studies ◽  
Band Region ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Cryostat Sections

Ca++-Mg++-dependent ATPase and calsequestrin, the major intrinsic and extrinsic proteins, respectively, of the sarcoplasmic reticulum, were localized in cryostat sections of adult rat skeletal muscle by immunofluorescent staining and phase-contrast microscopy. Relatively high concentrations of both the ATPase and calsequestrin were found in fast-twitch myofibers while a very low concentration of the ATPase and a moderate concentration of calsequestrin were found in slow-twitch myofibers. These findings are consistent with previous biochemical studies of the isolated sarcoplasmic reticulum of slow-twitch and fast-twitch mammalian muscles. The distribution of the ATPase in muscle fibers is distinctly different from that of calsequestrin. While calsequestrin is present only near the interface between the I- and A-band regions of the sarcomere, the ATPase is found throughout the I-band region as well as in the center of the A-band region. In comparing these results with in situ ultrastructural studies of the distribution of sarcoplasmic reticulum in fast-twitch muscle, it appears that the ATPase is rather uniformly distributed throughout the sarcoplasmic reticulum while calsequestrin is almost exclusively confined to those regions of the membrane system which correspond to terminal cisternae. Fluorescent staining with these antisera was not observed in vascular smooth muscle cells present in the cryostat sections of the mammalian skeletal muscle used in this study.

Effect of clenbuterol on sarcoplasmic reticulum function in single skinned mammalian skeletal muscle fibers

1998 ◽  
Vol 274 (6) ◽  
pp. C1718-C1726 ◽  
Author(s):  
Anthony J. Bakker ◽  
Stewart I. Head ◽  
Anthony C. Wareham ◽  
D. George Stephenson
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Rattus Norvegicus ◽  
Extensor Digitorum Longus ◽  
Muscle Fibers ◽  
Mammalian Skeletal Muscle ◽  
Direct Effects ◽  
Contraction Coupling ◽  
Slow Twitch

We examined the effect of the β2-agonist clenbuterol (50 μM) on depolarization-induced force responses and sarcoplasmic reticulum (SR) function in muscle fibers of the rat ( Rattus norvegicus; killed by halothane overdose) that had been mechanically skinned, rendering the β2-agonist pathway inoperable. Clenbuterol decreased the peak of depolarization-induced force responses in the extensor digitorum longus (EDL) and soleus fibers to 77.2 ± 9.0 and 55.6 ± 5.4%, respectively, of controls. The soleus fibers did not recover. Clenbuterol significantly and reversibly reduced SR Ca2+loading in EDL and soleus fibers to 81.5 ± 2.8 and 78.7 ± 4.0%, respectively, of controls. Clenbuterol also produced an ∼25% increase in passive leak of Ca2+ from the SR of the EDL and soleus fibers. These results indicate that clenbuterol has direct effects on fast- and slow-twitch skeletal muscle, in the absence of the β2-agonist pathway. The increased Ca2+ leak in the triad region may lead to excitation-contraction coupling damage in the soleus fibers and could also contribute to the anabolic effect of clenbuterol in vivo.

Biochemical adaptations in skeletal muscle of trained thyroidectomized rats

1976 ◽  
Vol 230 (5) ◽  
pp. 1194-1197 ◽  
Author(s):  
RL Terjung ◽  
JE Koerner
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome C ◽  
Training Program ◽  
Muscle Fibers ◽  
Oxidative Capacity ◽  
Treadmill Running ◽  
Absolute Increase ◽  
Normal Thyroid Function ◽  
Slow Twitch ◽  
Fast Twitch

The cytochrome c concentrations of the different types of skeletal muscle of trained and nontrained normal and thyroidectomized rats were measured. Animals were trained by treadmill running 1 mph, at a 15% incline, 1 h/day, 5 days/wk for at least 12 wk. This training program induced an expected 50% increase in cytochrome c in the high-oxidative fast-twitch red (FTR) and slow-twitch red (STR) fibers and only a 25% increase in the low-oxidative fast-twitch white (FTW) fibers of the normal rats. This same training program caused a greater increase (100%) in the FTR and STR fibers of the thyroidectomized runners and a dramatic 243% increase in the FTW fiber. Even though the thyroidectomy procedure caused a reduction in oxidative capacity of all types of skeletal muscle fibers to about one-half normal, the absolute increase in cytochrome c in the muscles of the trained thyroidectomized animals was essentially the same or greater than that of the normal trained animals. These results indicate that the adaptive response to training of an increased oxidative capacity in skeletal muscle occurs in the absence of normal thyroid function. They also suggest that the exercise bouts of the thyroidectomized animals were performed with a relatively greater involvement of the FTW muscle fibers.

scholarly journals Factors determining the subunit composition of tropomyosin in mammalian skeletal muscle

1985 ◽  
Vol 226 (2) ◽  
pp. 461-468 ◽  
Author(s):  
D H Heeley ◽  
G K Dhoot ◽  
S V Perry
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Reciprocal Relationship ◽  
Mammalian Skeletal Muscle ◽  
Adult Rat ◽  
Fast Twitch Muscle ◽  
Rat Soleus Muscle ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Developing Muscle

Adult rat fast-twitch skeletal muscle such as extensor digitorum longus contains alpha- and beta-tropomyosin subunits, as is the case in the corresponding muscles of rabbit. Adult rat soleus muscle contains beta-, gamma- and delta-tropomyosins, but no significant amounts of alpha-tropomyosin. Evidence for the presence of phosphorylated forms of at least three of the four tropomyosin subunit isoforms was obtained, particularly in developing muscle. Immediately after birth alpha- and beta-tropomyosins were the major components of skeletal muscle, in both fast-twitch and slow-twitch muscles. Differentiation into slow-twitch skeletal muscles was accompanied by a fall in the amount of alpha-tropomyosin subunit and its replacement with gamma- and delta-subunits. After denervation and during regeneration after injury, the tropomyosin composition of slow-twitch skeletal muscle changed to that associated with fast-twitch muscle. Thyroidectomy slowed down the changes in tropomyosin composition resulting from the denervation of soleus muscle. The results suggest that the ‘ground state’ of tropomyosin-gene expression in the skeletal muscle gives rise to alpha- and beta-tropomyosin subunits. Innervation by a ‘slow-twitch’ nerve is essential for the expression of the genes controlling gamma- and delta-subunits. There appears to be reciprocal relationship between expression of the gene controlling the synthesis of alpha-tropomyosin and those controlling the synthesis of gamma- and delta-tropomyosin subunits.

scholarly journals Neural regulation of parvalbumin expression in mammalian skeletal muscle

1986 ◽  
Vol 235 (1) ◽  
pp. 67-73 ◽  
Author(s):  
E Leberer ◽  
D Pette
Keyword(s):  
Skeletal Muscle ◽  
Motor Neuron ◽  
Tibialis Anterior Muscle ◽  
Neuron Activity ◽  
Adult Rabbit ◽  
Mammalian Skeletal Muscle ◽  
Rapid Reduction ◽  
Fast Twitch Muscle ◽  
Slow Twitch ◽  
Fast Twitch

Parvalbumin was purified from rabbit fast skeletal muscle and used to raise antibodies in sheep. Subsequently, a sensitive ‘sandwich’ enzyme-linked immunoadsorbent assay permitted quantification of parvalbumin in homogenates of embryonic, maturing, innervated, denervated and chronically stimulated skeletal muscles of the rabbit. High concentrations of parvalbumin were detected in various adult fast-twitch muscles of the rabbit (700-1200 micrograms/g of muscle), whereas slow-twitch muscles contained negligible concentrations (3-5 micrograms/g of muscle). Parvalbumin was not detectable in embryonic-rabbit muscles (21, 25, 28 days of gestation), either presumptive fast- or slow-twitch. However, parvalbumin concentrations did increase during postnatal development in presumptive fast-twitch muscles. Thus the onset of parvalbumin synthesis appears to be correlated with the neonatal-to-adult transition of motor-neuron activity [Navarrete & Vrbová (1983) Dev. Brain Res. 8, 11-19]. The increase of parvalbumin in maturing, presumptive fast-twitch muscle was suppressed by denervation. In the adult rabbit, denervation of the tibialis anterior muscle caused a reduction of parvalbumin to a level normally found in slow-twitch muscles. In contrast, the already low levels of parvalbumin in maturing and adult slow-twitch soleus muscle were unaffected by denervation. Chronic low-frequency stimulation of adult fast-twitch muscle resulted in a rapid reduction of parvalbumin to a level normally found in slow-twitch muscle. These data support the hypothesis that the expression of parvalbumin is under positive control of fast-type motor-neuron activity.

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