TEMPERATURE EFFECTS ON THE FORCE-FREQUENCY RELATIONSHIP IN SKELETAL MUSCLE IN VITRO

1999 ◽  
Vol 31 (Supplement) ◽  
pp. S221
Author(s):  
M. Rickett ◽  
W. Barnes ◽  
W. Cooke
Keyword(s):  
Skeletal Muscle ◽  
Temperature Effects ◽  
Force Frequency ◽  
Frequency Relationship

Dimethyl sulfoxide depresses skeletal muscle contractility

1994 ◽  
Vol 76 (5) ◽  
pp. 2186-2190 ◽  
Author(s):  
M. B. Reid ◽  
M. R. Moody
Keyword(s):  
Skeletal Muscle ◽  
Dimethyl Sulfoxide ◽  
Contractile Function ◽  
Dose Dependence ◽  
Detectable Effect ◽  
Force Frequency ◽  
Frequency Relationship ◽  
The Right ◽  
Dose Dependent

Dimethyl sulfoxide (DMSO) is commonly used in studies of skeletal muscle as a selective antioxidant (DMSO preferentially scavenges hydroxyl radicals) or as a solvent for drugs. The present experiments tested DMSO for direct effects on diaphragm contractile properties. Fiber bundles were removed from anesthetized rats, mounted in vitro at optimal length (37 degrees C), curarized, and stimulated directly. Protocol 1 tested for contractile depression and dose dependence by comparing bundles treated with DMSO (0.6–640 mM) with time- and stimulus-matched controls. Protocol 2 tested reversibility of 220 mM DMSO effects by using each bundle as its own control. DMSO decreased the relative forces developed during twitch and submaximal tetanic (30- and 60-Hz) contractions, shifting the force-frequency relationship down and to the right. These effects were strongly dose dependent and were reversed by DMSO washout. DMSO had no detectable effect on the forces developed during maximal tetany (200 Hz). DMSO depresses contractile function of diaphragm fibers by reversible dose-dependent inhibition of excitation-contraction coupling.

Abstract 15596: Maturation of Hipsc-cm Electrophysiological and Contractile Function for Enhanced Sensitivity of Cardiac Safety Assays

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Heather B Hayes ◽  
Anthony M Nicolini ◽  
Colin Arrowood ◽  
Daniel Millard
Keyword(s):  
Contractile Function ◽  
Induced Pluripotent Stem Cell ◽  
Force Frequency ◽  
Cardiac Safety ◽  
Electrophysiological Response ◽  
Mechanical Conditioning ◽  
Enhanced Sensitivity ◽  
Frequency Relationship ◽  
Positive Force

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have significantly advanced in vitro cardiac safety and disese modeling, yet remain an immature representation of human myocytes. Electrical or mechanical conditioning of hiPSC-CMs facilitates functional maturation, as measured by a positive force-frequency relationship, but current in vitro protocols require 2-4 weeks of conditioning. Using array-based contractility and local electrical stimulation, we detected functionally mature phenotypes and compound responses in hiPSC-CMs after only 48 hours of chronic pacing. To mature cardiomyocytes, hiPSC-CMs were cultured on 24- and 96-well MEA plates with a dedicated stimulation electrodes. Later, hiPSC-CMs were electrically or optically paced at 2Hz for 48 hours. Multimodal measures quantified contractile and electrophysiological responses to varied pacing rates and compound addition. After 48 hours of pacing, hiPSC-CMs displayed shortened repolarization timing compared to before chronic pacing (baseline: 423 +/- 21 ms; matured: 316 +/- 15 ms), without significant beat period changes (baseline: 1255 +/- 40 ms; matured: 1314 +/- 84 ms). Contractile beat amplitude was measured using array-based impedance during spontaneous beating and at increasing pacing rates (1, 1.2, 1.5, 2, and 2.5 Hz). Before chronic pacing, beat amplitude decreased with increasing pacing rate; after chronic pacing, the same wells displayed increased beat amplitudes with increasing pacing rate. The matured wells also showed enhanced sensitivity to positive inotropes, such as isoproterenol, digoxin, omecamtiv mecarbil, and dobutamine. Local extracellular action potentials (LEAP) further revealed altered electrophysiological response to ranolazine, a multichannel blocker. Unpaced control wells exhibited dose-dependent APD90 prolongation in response to ranolazine, whereas matured wells showed no APD90 change. Similar results were seen with 48 hour of optogenetic pacing at 2 Hz. Overall, hiPSC-CMs chronically paced for only 48 hours exhibited more mature functional phenotypes, including a positive force-frequnecy relationship, enhanced ionotrope sensitivity, and altered compound response.

Increased susceptibility to fatigue of slow- and fast-twitch muscles from mice lacking the MG29 gene

2000 ◽  
Vol 4 (1) ◽  
pp. 43-49 ◽  
Author(s):  
RAMAKRISHNAN Y. NAGARAJ ◽  
CHRISTOPHER M. NOSEK ◽  
MARCO A. P. BROTTO ◽  
MIYUKI NISHI ◽  
HIROSHI TAKESHIMA ◽  
...  
Keyword(s):  
Major Protein ◽  
Force Frequency ◽  
Wild Type ◽  
Membrane Structures ◽  
Intracellular Ca ◽  
Slow Twitch Muscle ◽  
Fast Twitch Muscle ◽  
Frequency Relationship ◽  
Fast Twitch

Mitsugumin 29 (MG29), a major protein component of the triad junction in skeletal muscle, has been identified to play roles in the formation of precise junctional membrane structures important for efficient signal conversion in excitation-contraction (E-C) coupling. We carried out several experiments to not only study the role of MG29 in normal muscle contraction but also to determine its role in muscle fatigue. We compared the in vitro contractile properties of three muscles types, extensor digitorum longus (EDL) (fast-twitch muscle), soleus (SOL) (slow-twitch muscle), and diaphragm (DPH) (mixed-fiber muscle), isolated from mice lacking the MG29 gene and wild-type mice prior to and after fatigue. Our results indicate that the mutant EDL and SOL muscles, but not DPH, are more susceptible to fatigue than the wild-type muscles. The mutant muscles not only fatigued to a greater extent but also recovered significantly less than the wild-type muscles. Following fatigue, the mutant EDL and SOL muscles produced lower twitch forces than the wild-type muscles; in addition, fatiguing produced a downward shift in the force-frequency relationship in the mutant mice compared with the wild-type controls. Our results indicate that fatiguing affects the E-C components of the mutant EDL and SOL muscles, and the effect of fatigue in these mutant muscles could be primarily due to an alteration in the intracellular Ca homeostasis.

Force potentiation in respiratory muscles: comparison of diaphragm and sternohyoid

1993 ◽  
Vol 264 (6) ◽  
pp. R1095-R1100 ◽  
Author(s):  
E. Van Lunteren ◽  
H. Vafaie
Keyword(s):  
Respiratory Muscle ◽  
Respiratory Muscles ◽  
Upper Airway ◽  
Rapid Onset ◽  
Force Frequency ◽  
Twitch Force ◽  
Twitch Potentiation ◽  
Early Portion ◽  
Frequency Relationship

Coordinated contraction of thoracic and pharyngeal upper airway respiratory muscles optimizes ventilation, whereas pharyngeal muscle dysfunction may lead to obstructive apneas during sleep. We hypothesized that the force potentiation exhibited by the pharyngeal respiratory muscle, the sternohyoid, in keeping with its faster contractile kinetics, would be greater than that of the thoracic respiratory muscle, the diaphragm. Rat muscles were studied in vitro at 37 degrees C with three force-potentiating protocols: posttetanic twitch potentiation, staircase phenomenon (twitch potentiation), and a classic fatigue paradigm. The sternohyoid had a faster isometric contraction time, a more rightward located force-frequency relationship, and both a more rapid onset and a greater degree of fatigue than the diaphragm. During the early portion of the fatigue protocols, the increase in force was significantly greater for the sternohyoid muscle than the diaphragm (e.g., 33 vs. 3% increase at 20 Hz, P < 0.005). During repetitive twitches at 2, 3, and 5 Hz (staircase test), sternohyoid muscle force increased more than diaphragm force at the higher stimulus frequencies (e.g., by 38 vs. 23% at 5 Hz, P < 0.01). After brief tetanic stimuli, sternohyoid twitch force increased more than diaphragm twitch force (e.g., 73 vs. 14% increase after 125 Hz tetanus, P < 0.005). These data indicate that force potentiation is exhibited by both diaphragm and sternohyoid respiratory muscles, but to different extents, when activated repetitively.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function

2014 ◽  
Vol 112 (4) ◽  
pp. 778-791 ◽  
Author(s):  
Jeffrey M. McManus ◽  
Hui Lu ◽  
Miranda J. Cullins ◽  
Hillel J. Chiel
Keyword(s):  
Motor Neuron ◽  
Muscle Activation ◽  
Retractor Muscle ◽  
Force Frequency ◽  
Additional Function ◽  
Jaw Muscle ◽  
Protraction Phase ◽  
Frequency Relationship

To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californica's feeding system. This muscle mediates retraction of Aplysia's food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38's activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38's typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysia's generation of multifunctionality.

Role of NO and PAF in the impairment of skeletal muscle contractility induced by TNF-α

2000 ◽  
Vol 279 (6) ◽  
pp. R2156-R2163 ◽  
Author(s):  
Giuseppe Alloatti ◽  
Claudia Penna ◽  
Filippo Mariano ◽  
Giovanni Camussi
Keyword(s):  
Skeletal Muscle ◽  
Methyl Ester ◽  
Platelet Activating Factor ◽  
Inhibitory Effect ◽  
No Production ◽  
Force Frequency ◽  
Muscle Contractility ◽  
Tnf Α ◽  
Frequency Relationship

The role of platelet-activating factor (PAF) and nitric oxide (NO) as mediators of the effects of tumor necrosis factor-α (TNF-α) on skeletal muscle contractility was studied in guinea pig extensor digitorum longus (EDL) muscle. TNF-α (5–10 ng/ml) reduced contractility at every stimulation frequency (1–200 Hz) and shifted the force-frequency relationship to the right. The role of NO and PAF as mediators of TNF-α was suggested by the protective effect of N G-nitro-l-arginine methyl ester (l-NAME; 1 mM), but not of N G-nitro-d-arginine methyl ester (d-NAME; 1 mM), and by the inhibitory effect of the PAF-receptor antagonist WEB-2170 (3 μM). TNF-α increased the production of PAF and NO. Similar to TNF-α, both S-nitroso- N-acetylpenicillamine (0.5–1 μM), an NO-generating compound, and PAF (10–20 nM) reduced EDL contractility. l-NAME, but not d-NAME, blocked the negative effect of PAF. Blockade of phospholipase A2, which is required for PAF synthesis, significantly reduced the effects of TNF-α. WEB-2170 inhibited NO synthesis induced by TNF-α and PAF-stimulated NO production. These results suggest that both PAF and NO contribute to the development of the mechanical alterations induced by TNF-α and that NO production is downstream to the synthesis of PAF.

Effects of N-acetylcysteine on in vitro diaphragm function are temperature dependent

1994 ◽  
Vol 77 (5) ◽  
pp. 2434-2439 ◽  
Author(s):  
P. T. Diaz ◽  
E. Brownstein ◽  
T. L. Clanton
Keyword(s):  
Skeletal Muscle ◽  
Salt Solution ◽  
Contractile Function ◽  
Recovery Period ◽  
Physiological Salt Solution ◽  
Force Frequency ◽  
Rat Diaphragm ◽  
Temperature Dependent ◽  
Diaphragm Function

Recent evidence has shown that systemic administration of N-acetylcysteine (NAC), a compound structurally similar to the intracellular antioxidant glutathione, inhibits skeletal muscle fatigue. To further elucidate the actions of NAC, we studied its effects on in vitro rat diaphragm contractile function. Rat diaphragm strips were incubated in tissue baths containing physiological salt solution (n = 29) or physiological salt solution containing 4 mg/ml of NAC (n = 29). Strips were stimulated by either indirect or direct means. After determination of baseline contractile characteristics, strips were fatigued for 4 min at 20 Hz (1 train/s, 0.33 ms train duration). Force-frequency relationships were then studied over a 60-min recovery period. We found that 1) NAC had significant effects on the baseline force-frequency relationship; treated strips had increased peak tension but diminished twitch tension and accelerated twitch kinetics; 2) NAC had significant fatigue-sparing effects that were magnified at 37 degrees C; and 3) NAC treatment did not improve postfatigue recovery. The effects of NAC were generally independent of the stimulation method. We conclude that NAC has direct temperature-dependent effects on diaphragm function. These effects are consistent with the properties of NAC as an antioxidant and suggest important but complex effects of oxidant stress on skeletal muscle.

Effect of spaceflight on skeletal muscle: mechanical properties and myosin isoform content of a slow muscle

1994 ◽  
Vol 76 (4) ◽  
pp. 1764-1773 ◽  
Author(s):  
V. J. Caiozzo ◽  
M. J. Baker ◽  
R. E. Herrick ◽  
M. Tao ◽  
K. M. Baldwin
Keyword(s):  
Skeletal Muscle ◽  
De Novo ◽  
Fiber Type ◽  
Microgravity Environment ◽  
Type I ◽  
Force Frequency ◽  
Slow Type ◽  
Force Velocity ◽  
Flight Muscles ◽  
Frequency Relationship

This study examined changes in contractile, biochemical, and histochemical properties of slow antigravity skeletal muscle after a 6-day spaceflight mission. Twelve male Sprague-Dawley rats were randomly divided into two groups: flight and ground-based control. Approximately 3 h after the landing, in situ contractile measurements were made on the soleus muscles of the flight animals. The control animals were studied 24 h later. The contractile measurements included force-velocity relationship, force-frequency relationship, and fatigability. Biochemical measurements focused on the myosin heavy chain (MHC) and myosin light chain profiles. Adenosine-triphosphatase histochemistry was performed to identify cross-sectional area of slow and fast muscle fibers and to determine the percent fiber type distribution. The force-velocity relationships of the flight muscles were altered such that maximal isometric tension (Po) was decreased by 24% and maximal shortening velocity was increased by 14% (P < 0.05). The force-frequency relationship of the flight muscles was shifted to the right of the control muscles. At the end of the 2-min fatigue test, the flight muscles generated only 34% of Po, whereas the control muscles generated 64% of Po. The flight muscles exhibited de novo expression of the type IIx MHC isoform as well as a slight decrease in the slow type I and fast type IIa MHC isoforms. Histochemical analyses of flight muscles demonstrated a small increase in the percentage of fast type II fibers and a greater atrophy of the slow type I fibers. The results demonstrate that contractile properties of slow antigravity skeletal muscle are sensitive to the microgravity environment and that changes begin to occur within the 1st wk. These changes were at least, in part, associated with changes in the amount and type of contractile protein expressed.

N-acetylcysteine administration and loaded breathing

1995 ◽  
Vol 79 (1) ◽  
pp. 340-347 ◽  
Author(s):  
G. S. Supinski ◽  
D. Stofan ◽  
R. Ciufo ◽  
A. DiMarco
Keyword(s):  
Respiratory Failure ◽  
Respiratory Arrest ◽  
Diaphragm Muscle ◽  
Glutathione Metabolism ◽  
Limiting Factor ◽  
Force Frequency ◽  
Respiratory Muscle Fatigue ◽  
Loaded Breathing ◽  
Frequency Relationship

Recent work has shown that loaded breathing produces alterations in diaphragmatic glutathione metabolism. Moreover, it has been suggested that alterations in glutathione levels may be related to the development of respiratory muscle fatigue and respiratory failure during loading. The purpose of this study was to determine whether it was possible to augment diaphragmatic stores of reduced glutathione (GSH) and thereby delay the development of respiratory failure during loaded breathing by administering N-acetylcysteine (NAC), a glutathione precursor. We compared the effects of massive inspiratory loading on saline- and NAC-treated groups of decerebrate unanesthetized rats with loading continuing until respiratory arrest occurred. As controls, we also studied unloaded saline- and NAC-treated animals. After arrest, diaphragms were excised, measurement was made of diaphragmatic GSH and oxidized glutathione (GSSG) concentrations, and assessment was made of in vitro diaphragmatic contractility (i.e., the force-frequency relationship and in vitro fatigability). We found that loading of saline-treated animals produced reductions in the diaphragmatic force-frequency curve, reductions in GSH, and increases in GSSG levels. NAC administration blunted loading-induced decreases in diaphragmatic GSH levels and reduced the in vitro fatigability of excised diaphragm muscle strips. NAC did not significantly alter the time to respiratory arrest, however, and also failed to alter the effect of loaded breathing on the diaphragmatic force-frequency relationship. These findings suggest that free radical-mediated GSH depletion is not the limiting factor determining the development of respiratory failure in this model of loaded breathing.

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