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Investigative Ophthalmology & Visual... Jul 2021Mutations in the fibroblast growth factor (FGF) receptor can result in strabismus, but little is known about how FGFs affect extraocular muscle structure and function.... (Comparative Study)
Comparative Study
PURPOSE
Mutations in the fibroblast growth factor (FGF) receptor can result in strabismus, but little is known about how FGFs affect extraocular muscle structure and function. These were assessed after short-term and long-term exposure to exogenously applied FGF2 to determine the effect of enhanced signaling.
METHODS
One superior rectus muscle of adult rabbits received either a series of three injections of 500 ng, 1 µg, or 5 µg FGF2 and examined after 1 week, or received sustained treatment with FGF2 and examined after 1, 2, or 3 months. Muscles were assessed for alterations in force generation, myofiber size, and satellite cell number after each treatment.
RESULTS
One week after the 5 µg FGF2 injections, treated muscles showed significantly increased force generation compared with naïve controls, which correlated with increased myofiber cross-sectional areas and Pax7-positive satellite cells. In contrast, 3 months of sustained FGF2 treatment resulted in decreased force generation, which correlated with decreased myofiber size and decreased satellite cells compared with naïve control and the untreated contralateral side.
CONCLUSIONS
FGF2 had distinctly different effects when short-term and long-term treatments were compared. The decreased size and ability to generate force correlated with decreased myofiber areas seen in individuals with Apert syndrome, where there is sustained activation of FGF signaling. Knowing more about signaling pathways critical for extraocular muscle function, development, and disease will pave the way for improved treatment options for strabismus patients with FGF abnormalities in craniofacial disease, which also may be applicable to other strabismus patients.
Topics: Animals; Fibroblast Growth Factor 2; Injections, Intramuscular; Models, Animal; Muscle Contraction; Muscle Fibers, Skeletal; Oculomotor Muscles; Rabbits
PubMed: 34293078
DOI: 10.1167/iovs.62.9.34 -
Journal of Applied Physiology... May 2022This study investigated the effects of postactivation potentiation (PAP) on the force output and muscle architecture in plantar flexor muscles. The mechanical response...
This study investigated the effects of postactivation potentiation (PAP) on the force output and muscle architecture in plantar flexor muscles. The mechanical response to a single electrical stimulus (twitch) and to two (doublet) and three (triplet) stimuli (10-ms interpulse interval) was measured before and after a 6-s maximal voluntary contraction (MVC). Ultrasound imaging was used to measure fascicle length and pennation angle of the gastrocnemius medialis at rest and during the electrically induced contractions. Immediately after the conditioning MVC, twitch peak force (+40%) and its maximal rate of force development (+57%) and relaxation (+62%) were greater than before the MVC ( < 0.001). The PAP extent was less for the doublet than for the twitch and for the triplet than for the doublet ( < 0.05). Whereas none of the architectural parameters changed at rest, fascicle shortening and increase in pennation angle during contractions were greater after than before the conditioning MVC, with a greater extent ( < 0.001) during the twitch (+28% and +58%, respectively) compared with the doublet (+16% and +36%) and the triplet (+12% and +14%). Overall, our results indicate that the effect of the conditioning MVC on mechanical output and muscle architecture decreased from the twitch to the triplet in plantar flexor muscles. The decreased PAP observed during doublet and triplet compared with twitch indicates that the benefit of this mechanism to the enhancement of muscle performance becomes progressively less effective during successive muscle activation. Postactivation potentiation (PAP), a form of activity-dependent potentiation, is defined as the acute enhancement of muscle contractile properties induced by a conditioning contraction, usually a maximal voluntary contraction. The purpose of our study was to investigate the effects of PAP on force production and muscle architecture in plantar flexor (PF) muscles. The results indicate that the extent of PAP decreased from the twitch to the triplet in PF muscles. Furthermore, this study shows that fascicle shortening and the increase in pennation angle were greater after the maximal voluntary contraction for the twitch, the doublet, and the triplet, with more pronounced effects for the twitch.
Topics: Isometric Contraction; Muscle Contraction; Muscle, Skeletal; Ultrasonography
PubMed: 35358400
DOI: 10.1152/japplphysiol.00359.2021 -
British Journal of Pharmacology Apr 19981. The effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), alpha,beta-methylene-ATP (alpha,beta-MeATP) and 2-methylthio-ATP (2-MeSATP) on...
1. The effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), alpha,beta-methylene-ATP (alpha,beta-MeATP) and 2-methylthio-ATP (2-MeSATP) on longitudinally orientated smooth muscle strips from marmoset urinary bladder were investigated by use of standard organ bath techniques. 2. After being mounted in superfusion organ baths, 66.7% (n=249) of marmoset detrusor smooth muscle strips developed spontaneous tone, 48.2% of all strips examined developed tone equivalent to greater than 0.1 g mg(-1) of tissue and were subsequently utilized in the present investigation. 3. On exposure to ATP, muscle strips exhibited a biphasic response, a rapid and transient contraction followed by a more prolonged relaxation. Both responses were found to be concentration-dependent. ADP and 2-MeSATP elicited a similar response (contraction followed by relaxation), whereas application of alpha,beta-MeATP only produced a contraction. The potency order for each effect was alpha,beta-MeATP> >2-MeSATP> ATP>ADP (contractile response) and ATP=2-MeSATP> or = ADP> > alpha,beta-MeATP (relaxational response). 4. Desensitization with alpha,beta-MeATP (10 microM) abolished the contractile phase of the response to ATP, but had no effect on the level of relaxation evoked by this agonist. On the other hand, the G-protein inactivator, GDPbetaS (100 microM) abolished only the relaxation response to ATP. Suramin (general P2 antagonist, 100 microM) shifted both the contractile and relaxation ATP concentration-response curves to the right, whereas cibacron blue (P2Y antagonist, 10 microM) only antagonized the relaxation response to ATP. In contrast, the adenosine receptor antagonist, 8-phenyltheophylline (10 microM), had no effect on the relaxation response curve to ATP. 5. Incubation with tetrodotoxin (TTX, 3 microM) or depolarization of the muscle strip with 40 mM K+ Krebs failed to abolish the relaxation to ATP. In addition, neither Nomega-nitro-L-arginine (L-NOARG, 10 microM) nor methylene blue (10 microM) had any effect on the relaxation response curve. However, tos-phe-chloromethylketone (TPCK, 3 microM), an inhibitor of cyclicAMP-dependent protein kinase A (PKA), significantly (P<0.01) shifted the curve for the ATP-induced relaxation to the right. 6. It is proposed that marmoset detrusor smooth muscle contains two receptors for ATP, a classical P2X-type receptor mediating smooth muscle contraction, and a P2Y (G-protein linked) receptor mediating smooth muscle relaxation. The results also indicate that the ATP-evoked relaxation may occur through the activation of cyclicAMP-dependent PKA.
Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Callithrix; Female; In Vitro Techniques; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Receptors, Purinergic; Receptors, Purinergic P1; Receptors, Purinergic P2; Urinary Bladder
PubMed: 9605564
DOI: 10.1038/sj.bjp.0701774 -
British Journal of Pharmacology Apr 2006The peptide ligand neuromedin U (NMU) has been implicated in an array of biological activities, including contraction of uterine, intestinal and urinary bladder smooth...
The peptide ligand neuromedin U (NMU) has been implicated in an array of biological activities, including contraction of uterine, intestinal and urinary bladder smooth muscle. However, many of these responses appear to be species-specific. This study was undertaken to fully elucidate the range of smooth muscle-stimulating effects of NMU in rats, mice and guinea-pigs, and to examine the extent of the species differences. In addition, the NMU1 receptor knockout mouse was used to determine which receptor subtype mediates the contractile responses generated by NMU in the mouse. A range of isolated organ in vitro bioassays were carried out, which were chosen to re-confirm previous literature reports (uterine and stomach fundus contraction) and also to explore potentially novel smooth muscle responses to NMU. This investigation uncovered a number of previously unidentified NMU-mediated responses: contraction of rat lower esophageal sphinster (LES), rat ileum, mouse gallbladder, enhancement of electrically evoked contractions in rat and mouse vas deferens, and a considerable degree of cross-species differences. Studies using the NMU1 receptor knockout mice revealed that in the mouse fundus and gallbladder assays the NMU contractile response was mediated entirely through the NMU1 receptor subtype, whereas, in assays of mouse uterus and vas deferens, the response to NMU was unchanged in the NMU1 receptor knockout mouse, suggesting that the NMU response may be mediated through the NMU2 receptor subtype. NMU receptor subtype-selective antagonists are required to further elucidate the role of the individual receptor subtypes.
Topics: Animals; Female; Guinea Pigs; Male; Membrane Proteins; Mice; Mice, Knockout; Muscle Contraction; Muscle, Smooth; Neuropeptides; Rats; Rats, Sprague-Dawley; Receptors, Neurotransmitter
PubMed: 16474416
DOI: 10.1038/sj.bjp.0706677 -
The Journal of Physiology Apr 2022A. V. Hill was awarded the 1922 Nobel Prize, jointly with Otto Meyerhof, for Physiology or Medicine for his work on energetic aspects of muscle contraction. Hill used...
A. V. Hill was awarded the 1922 Nobel Prize, jointly with Otto Meyerhof, for Physiology or Medicine for his work on energetic aspects of muscle contraction. Hill used his considerable mathematical and experimental skills to investigate the relationships among muscle mechanics, biochemistry and heat production. The main ideas of the work for which the Nobel Prize was awarded were superseded within a decade, and the legacy of Hill and Meyerhof's Nobel work was not a set of persistent, influential ideas but rather a prolonged period of extraordinary activity that advanced the understanding of how muscles work far beyond the concepts that led to the Nobel Prize. Hill pioneered the integration of mathematics into the study of physiology and pharmacology. Particular aspects of Hill's own work that remain in common use in muscle physiology include mathematical descriptions of the relationships between muscle force output and shortening velocity and between force output and calcium concentration, and the model of muscle as a contractile element in series with an elastic element. We describe some of the characteristics of Hill's broader scientific activities and then outline how Hill's work on muscle energetics was extended after 1922, as a result of Hill's own work and that of others, to the present day.
Topics: Muscle Contraction; Muscles; Nobel Prize
PubMed: 35114037
DOI: 10.1113/JP281556 -
Scandinavian Journal of Medicine &... Feb 2023Walking and running are based on rapid burst-like muscle contractions. Burst-like contractions generate a Gaussian-shaped force profile, in which neuromuscular...
Walking and running are based on rapid burst-like muscle contractions. Burst-like contractions generate a Gaussian-shaped force profile, in which neuromuscular determinants have never been assessed. We investigated the neural and contractile determinants of the rate of force development (RFD) in burst-like isometric knee extensions. Together with maximal voluntary force (MVF), voluntary and electrically evoked (8 stimuli at 300 Hz, octets) forces were measured in the first 50, 100, and 150 ms of burst-like quadriceps contractions in 24 adults. High-density surface electromyography (HDsEMG) was adopted to measure the root mean square (RMS) and muscle fiber conduction velocity (MFCV) from the vastus lateralis and medialis. The determinants of voluntary force at 50, 100, and 150 ms were assessed by stepwise multiple regression analysis. Force at 50 ms was explained by RMS (R = 0.361); force at 100 ms was explained by octet (R = 0.646); force at 150 ms was explained by MVF (R = 0.711) and octet (R = 0.061). Peak RFD (which occurred at 60 ± 10 ms from contraction onset) was explained by MVF (R = 0.518) and by RMS (R = 0.074). MFCV did not emerge as a determinant of RFD. Muscle excitation was the sole determinant of early RFD (50 ms), while contractile characteristics were more relevant for late RFD (≥100 ms). As peak RFD is mostly determined by MVF, it may not be more informative than MVF itself. Therefore, a time-locked analysis of RFD provides more insights into the neuromuscular characteristics of explosive contractions.
Topics: Adult; Humans; Isometric Contraction; Muscle Contraction; Knee; Knee Joint; Electromyography; Muscle, Skeletal
PubMed: 36229231
DOI: 10.1111/sms.14244 -
American Journal of Physiology.... Jul 2022Although heat exposure has been shown to increase the skeletal rate of force development (RFD), the underlying processes remain unknown. This study investigated the...
Although heat exposure has been shown to increase the skeletal rate of force development (RFD), the underlying processes remain unknown. This study investigated the effect of heat on gastrocnemius medialis (GM) muscle-tendon properties and interactions. Sixteen subjects performed electrically evoked and voluntary contractions combined with ultrafast ultrasound under thermoneutral [control (CON): 25.8 ± 1.8°C, core temperature 37.0 ± 0.3°C, muscle temperature 34.0 ± 1.1°C] and passive heat exposure [hot (HOT): 47.4 ± 1.8°C, core temperature 38.4 ± 0.3°C, muscle temperature 37.0 ± 0.8°C] conditions. Maximal voluntary force changes did not reach statistical significance (-5.0 ± 11.3%, = 0.052) whereas voluntary activation significantly decreased (-4.6 ± 8.7%, = 0.038) in HOT. Heat exposure significantly increased voluntary RFD before 100 ms from contraction onset (+48.2 ± 62.7%; = 0.013), without further changes after 100 ms. GM fascicle dynamics during electrically evoked and voluntary contractions remained unchanged between conditions. Joint velocity at a given force was higher in HOT (+7.1 ± 6.6%; = 0.004) but the fascicle force-velocity relationship remained unchanged. Passive muscle stiffness and active tendon stiffness were lower in HOT than CON ( ≤ 0.030). This study showed that heat-induced increases in early voluntary RFD may not be attributed to changes in contractile properties. Late voluntary RFD was unaltered, possibly due to decreased soft tissues' stiffness in heat. Further investigations are required to explore the influence of neural drive and motor unit recruitment in the enhancement of explosive strength elicited by heat exposure.
Topics: Humans; Isometric Contraction; Muscle Contraction; Muscle, Skeletal; Tendons; Ultrasonography
PubMed: 35579335
DOI: 10.1152/ajpregu.00280.2021 -
Journal of Applied Physiology... Aug 2003Communication among scientists must be clear and concise to avoid ambiguity and misinterpretations. The selection of words must be based on accepted definitions. The... (Review)
Review
Communication among scientists must be clear and concise to avoid ambiguity and misinterpretations. The selection of words must be based on accepted definitions. The fields of biomechanics, muscle physiology, and exercise science have had a particularly difficult time with terminology, arising from the complexity of muscle contractions and by the use of inappropriate terminology by scientists. The dictionary definition of the verb "contract," specifically for the case of muscle, is "to undergo an increase in tension, or force, and become shorter." Under all circumstances, an activated muscle generates force, but an activated muscle generating force does not invariably shorten! During the 1920s and 1930s, investigators recognized that the interaction between the force generated by the muscle and the load on the muscle results in either shortening, no length change (isometric), or lengthening of the muscle. The recognition that muscles perform three different types of "contractions" required that contraction be redefined as "to undergo activation and generate force." Modifiers of contraction are then needed to clarify the lack of movement or the directionality of movement. Despite the contradiction, for 75 years the lack of movement has been termed an "isometric contraction." The directionality of the movement is then best described by the adjectives "shortening" and "lengthening." The definitions of "concentric" as "having the same center" and of "eccentric" as "not having the same center" are consistent with hypertrophy, or remodeling of the heart muscle, but are inappropriate to describe the contractions of skeletal muscles.
Topics: Animals; Humans; Isometric Contraction; Muscle Contraction; Terminology as Topic
PubMed: 12851415
DOI: 10.1152/japplphysiol.00280.2003 -
Journal of Electromyography and... Aug 2022We analyzed the time course of changes in muscle activity of the prime mover and synergist muscles during a sustained brake-pulling action and investigated the...
We analyzed the time course of changes in muscle activity of the prime mover and synergist muscles during a sustained brake-pulling action and investigated the relationship between muscle activity and braking force fluctuation (FF). Thirty-two participants performed a continuous fatiguing protocol (CFP) at 30% of maximal voluntary contraction (MVC) until failure. Surface electromyography was used to analyze root mean square (RMS) values in the flexor digitorum superficialis (FD), flexor carpi radialis (FC), extensor digitorum communis (ED), extensor carpi radialis (EC), brachioradialis (BR), biceps brachii (BB), and triceps brachii (TB). The FF and RMS in all muscles increased progressively (P<0.01) during the CFP, with sharp increments at time limit particularly in FD and FC (P<0.001). The RMS of the FD and FC were comparable to the baseline MVC values at time limit, in comparison to the other muscles that did not reach such levels of activity (P<0.003). The three flexor/extensor ratios used to measure coactivation levels decreased significantly (P<0.001). In contrast to RMS, MVC was still depressed at the minute 10 of recovery. The results suggest that the time limit was mainly constrained by fatigue-related mechanisms of the FD and FC but not by those of other synergist and antagonist muscles.
Topics: Electromyography; Fatigue; Gestures; Humans; Isometric Contraction; Muscle Contraction; Muscle Fatigue; Muscle, Skeletal
PubMed: 35717829
DOI: 10.1016/j.jelekin.2022.102677 -
The Journal of Physiology Oct 19671. Conditions are defined which determine the level of catch after acetylcholine stimulation of Mytilus muscle.2. Catch tension in dissected muscle is absent when...
1. Conditions are defined which determine the level of catch after acetylcholine stimulation of Mytilus muscle.2. Catch tension in dissected muscle is absent when connexions with ganglia are intact.3. Catch tension is absent at temperatures above 30 degrees C.4. Catch tension decreases when intervals between stimuli are increased.5. Increasing concentrations of 5-hydroxytryptamine (5-HT) from 10(-8)M to 10(-6)M quantitatively decreases catch tension.6. The length-tension curve of ganglion-free Mytilus muscle bundles suggests that catch tension varies in proportion to the tension developed in contraction.7. External Ca(2+) concentration has no selective influence on catch.8. All factors which reduce catch also increase muscle excitability, suggesting that catch may depend on a mechanism controlling the intracellular concentration of an activator such as Ca(2+).
Topics: Acetylcholine; Animals; Calcium; In Vitro Techniques; Mollusca; Muscle Contraction; Muscle, Smooth; Neuromuscular Junction; Serotonin; Temperature
PubMed: 6059005
DOI: 10.1113/jphysiol.1967.sp008335