← Back to Search
Cellular Mechanisms Of Fatigue In Skeletal Muscle.
H. Westerblad, J. Lee, J. Lännergren, D. Allen
Published 1991 · Chemistry, Medicine
Download PDFAnalyze on Scholarcy
Prolonged activation of skeletal muscle leads to a decline of force production known as fatigue. In this review we outline the ionic and metabolic changes that occur in muscle during prolonged activity and focus on how these changes might lead to reduced force. We discuss two distinct types of fatigue: fatigue due to continuous high-frequency stimulation and fatigue due to repeated tetanic stimulation. The causes of force decline are considered under three categories: 1) reduced Ca2+ release from the sarcoplasmic reticulum, 2) reduced myofibrillar Ca2+ sensitivity, and 3) reduced maximum Ca(2+)-activated tension. Reduced Ca2+ release can be due to impaired action potential propagation in the T tubules, and this is a principal cause of the tension decline with continuous tetanic stimulation. Another type of failing Ca2+ release, which is homogeneous across the fibers, is prominent with repeated tetanic stimulation; the underlying mechanisms of this reduction are not fully understood, although several possibilities emerge. Changes in intracellular metabolites, particularly increased concentration of Pi and reduced pH, lead to reduced Ca2+ sensitivity and reduced maximum tension, which make an important contribution to the force decline, especially with repeated tetanic stimulation.
This paper references
The effect of beta 2-adrenoceptor activation on ion-shifts and fatigue in mouse soleus muscles stimulated in vitro.
C. Juel (1988)
Force and membrane potential during and after fatiguing, continuous high-frequency stimulation of single Xenopus muscle fibres.
J. Lännergren (1986)
Calcium‐activated force responses in fast‐ and slow‐twitch skinned muscle fibres of the rat at different temperatures.
D. Stephenson (1981)
Voluntary strength and fatigue
P. Merton (1954)
Myosin isoenzymes in single muscle fibres of Xenopus laevis: analysis of five different functional types
J. Lännergren (1984)
Intracellular calcium and tension during fatigue in isolated single muscle fibres from Xenopus laevis.
D. Allen (1989)
Changes in muscle contractile properties and neural control during human muscular fatigue
B. Bigland-ritchie (1984)
The effect of sudden changes in ionic concentrations on the membrane potential of single muscle fibres
A. Hodgkin (1960)
Maximum tension and force‐velocity properties of fatigued, single Xenopus muscle fibres studied by caffeine and high K+.
J. Lännergren (1989)
Ryanodine receptor of skeletal muscle is a gap junction-type channel.
J. Ma (1988)
Voltage Dependent Charge Movement in Skeletal Muscle: a Possible Step in Excitation–Contraction Coupling
M. Schneider (1973)
The relation between force and intracellular pH in fatigued, single Xenopus muscle fibres.
H. Westerblad (1988)
Effect of rigor and cycling cross-bridges on the structure of troponin C and on the Ca2+ affinity of the Ca2+-specific regulatory sites in skinned rabbit psoas fibers.
K. Gueth (1987)
Greater hydrogen ion‐induced depression of tension and velocity in skinned single fibres of rat fast than slow muscles.
J. Metzger (1987)
Activation of the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum by caffeine and related compounds.
E. Rousseau (1988)
Single channel measurements of the calcium release channel from skeletal muscle sarcoplasmic reticulum. Activation by Ca2+ and ATP and modulation by Mg2+
J. S. Smith (1986)
Muscular fatigue investigated by phosphorus nuclear magnetic resonance
M. J. Dawson (1978)
It is diprotonated inorganic phosphate that depresses force in skinned skeletal muscle fibers.
T. Nosek (1987)
Calcium transients in isolated amphibian skeletal muscle fibres: detection with aequorin.
J. R. Blinks (1978)
Reconstruction of the action potential of frog sartorius muscle
R. Adrian (1973)
Mechanical relaxation rate and metabolism studied in fatiguing muscle by phosphorus nuclear magnetic resonance.
M. J. Dawson (1980)
Slowing of relaxation during fatigue in single mouse muscle fibres.
H. Westerblad (1991)
Lactate release in relation to tissue lactate in human skeletal muscle during exercise.
L. Jorfeldt (1978)
Inhibition of the Activation and Troponin Calcium Binding of Dog Cardiac Myofibrils by Acidic pH
E. Blanchard (1984)
Substrate utilization and enzymes in skeletal muscle of extremely endurance-trained men.
E. Jansson (1987)
The effect of temperature and stimulation scheme on fatigue and recovery in Xenopus muscle fibres.
J. Lännergren (1988)
Purified ryanodine receptor from skeletal muscle sarcoplasmic reticulum is the Ca2+-permeable pore of the calcium release channel.
T. Imagawa (1987)
Diet, muscle glycogen and physical performance.
J. Bergström (1967)
Biochemistry and biophysics of excitation-contraction coupling.
S. Fleischer (1989)
Motor drive and metabolic responses during repeated submaximal contractions in humans.
N. Vøllestad (1988)
Developmental and functional adaptation of contractile proteins in cardiac and skeletal muscles.
B. Swynghedauw (1986)
Tension restoration with caffeine in fatigued Xenopus muscle fibres of various types.
H. Westerblad (1987)
Myocardial contractile function during ischemia and hypoxia.
D. Allen (1987)
Fatigue of long duration in human skeletal muscle after exercise.
R. Edwards (1977)
Relaxation of vertebrate skeletal muscle. A synthesis of the biochemical and physiological approaches.
J. M. Gillis (1985)
Primary structure of the receptor for calcium channel blockers from skeletal muscle
T. Tanabe (1987)
Types of Muscle Fibres in Toad Skeletal Muscle
J. Lännergren (1966)
Fatigue of intermittent submaximal voluntary contractions: central and peripheral factors.
B. Bigland-ritchie (1986)
Changes in force and stiffness induced by fatigue and intracellular acidification in frog muscle fibres.
K. A. Edman (1990)
Composition of vacuoles and sarcoplasmic reticulum in fatigued muscle: electron probe analysis.
H. Gonzalez-serratos (1978)
Changes of intracellular milieu with fatigue or hypoxia depress contraction of skinned rabbit skeletal and cardiac muscle.
R. Godt (1989)
Calcium release in skinned muscle fibres of the toad by transverse tubule depolarization or by direct stimulation.
G. Lamb (1990)
Purification and reconstitution of the calcium release channel from skeletal muscle
F. Lai (1988)
Physiological types and histochemical profiles in motor units of the cat gastrocnemius
R. Burke (1973)
Detection, characterisation, and quantification of carnosine and other histidyl derivatives in cardiac and skeletal muscle.
J. J. O'Dowd (1988)
Effects of pH on contraction of rabbit fast and slow skeletal muscle fibers.
P. B. Chase (1988)
Purified ryanodine receptor of skeletal muscle sarcoplasmic reticulum forms Ca2+-activated oligomeric Ca2+ channels in planar bilayers.
L. Hymel (1988)
Involvement of dihydropyridine receptors in excitation–contraction coupling in skeletal muscle
E. Ríos (1987)
The effect of lactate on intracellular pH and force recovery of fatigued sartorius muscles of the frog, Rana pipiens.
Jean Marc Renaud (1989)
Changes in tetanic and resting [Ca2+]i during fatigue and recovery of single muscle fibres from Xenopus laevis.
J. Lee (1991)
The absence of neuromuscular transmission failure in sustained maximal voluntary contractions.
B. Bigland-ritchie (1982)
Speed of repolarization and morphology of glycerol‐treated frog muscle fibre
S. Nakajima (1973)
Kinetics of rapid Ca2+ release by sarcoplasmic reticulum. Effects of Ca2+, Mg2+, and adenine nucleotides.
G. Meissner (1986)
The effect of myosin phosphorylation on the contractile properties of skinned rabbit skeletal muscle fibers.
A. Persechini (1985)
The effect of metabolic inhibitors on the fatigue of the action potential in single muscle fibres
H. Lüttgau (1965)
The effects of inorganic phosphate and creatine phosphate on force production in skinned muscles from rat ventricle.
J. Kentish (1986)
The effects of ADP and phosphate on the contraction of muscle fibers.
R. Cooke (1985)
Movements of Na and K in single muscle fibres
A. Hodgkin (1959)
Flash photolysis studies of excitation-contraction coupling, regulation, and contraction in smooth muscle.
A. Somlyo (1990)
Is the change in intracellular pH during fatigue large enough to be the main cause of fatigue?
Jean Marc Renaud (1986)
Properties of caffeine- and potassium-contractures in fatigued frog single twitch muscle fibers.
H. Kanaya (1983)
Excitation frequency and muscle fatigue: Mechanical responses during voluntary and stimulated contractions
D. A. Jones (1979)
Selective glycogen depletion pattern in human muscle fibres after exercise of varying intensity and at varying pedalling rates
P. Gollnick (1974)
Influence of temperature upon contractile activation and isometric force production in mechanically skinned muscle fibers of the frog
R. Godt (1982)
Action potential fatigue in single skeletal muscle fibres of Xenopus.
J. Lännergren (1987)
Sarcoplasmic reticulum contains adenine nucleotide-activated calcium channels
J. S. Smith (1985)
The dependence of force and shortening velocity on substrate concentration in skinned muscle fibres from Rana temporaria.
M. Ferenczi (1984)
Correlated reduction of velocity of shortening and the rate of energy utilization in mouse fast-twitch muscle during a continuous tetanus
M. Crow (1983)
Fatigue of maintained voluntary muscle contraction in man
J. Stephens (1972)
The inhibition of rabbit skeletal muscle contraction by hydrogen ions and phosphate.
R. Cooke (1988)
Potassium and ionic strength effects on the isometric force of skinned twitch muscle fibres of the rat and toad.
R. Fink (1986)
Effect of cross-bridge kinetics on apparent Ca2+ sensitivity
P. Brandt (1982)
Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiace and skeletal muscles.
A. Fabiato (1978)
Actions of caffeine on fast‐ and slow‐twitch muscles of the rat.
M. W. Fryer (1989)
Transmission and contraction fatigue of rat motor units in relation to succinate dehydrogenase activity of motor unit fibres.
E. Kugelberg (1979)
Changes in motoneurone firing rates during sustained maximal voluntary contractions.
B. Bigland-ritchie (1983)
Intracellular pH and bicarbonate concentration in human muscle during recovery from exercise.
K. Sahlin (1978)
The gating behavior of a channel for Ca2+-induced Ca2+ release in fragmented sarcoplasmic reticulum.
H. Morii (1983)
Proposed Mechanism of Force Generation in Striated Muscle
A. Huxley (1971)
Force decline due to fatigue and intracellular acidification in isolated fibres from mouse skeletal muscle.
J. Lännergren (1991)
Purification of the ryanodine receptor and identity with feet structures of junctional terminal cisternae of sarcoplasmic reticulum from fast skeletal muscle.
M. Inui (1987)
Intracellular pH recovery and lactate efflux in mouse soleus muscles stimulated in vitro: the involvement of sodium/proton exchange and a lactate carrier.
C. Juel (1988)
Metabolic correlates of fatigue and of recovery from fatigue in single frog muscle fibers
V. Nassar-Gentina (1978)
Low-frequency fatigue in isolated skeletal muscles and the effects of methylxanthines.
D. Jones (1982)
This paper is referenced by
Ryanodine binding sites measured in small skeletal muscle biopsies.
P. Lunde (1997)
Fiber type and temperature dependence of inorganic phosphate: implications for fatigue.
E. Debold (2004)
Reduced power output in skeletal muscles devoid of skMLCK: RLC phosphorylation contributes to peak performance
Joshua Bowslaugh (2016)
A physiological perspective: Electrical stimulation of post-mortem muscle
Paula I. Fuller (2016)
Improving Neuroprosthesis-Assisted Standing with Nerve-Based Stimulating Electrodes
L. Fisher (2012)
Trimetazidine Reduces Basal Cytosolic Ca2+ Concentration During Hypoxia in Single Xenopus Skeletal Myocytes
C. Stary (2003)
Prolonged exercise potentiates sarcoplasmic reticulum Ca2+ uptake in rat diaphragm
S. Stavrianeas (2003)
II Substratutilisation (muskulärer Energiestoffwechsel)
G. Smekal (2004)
Mechanisms of functional loss in patients with chronic lung disease.
N. MacIntyre (2008)
Time‐of‐Day Effects on Myoelectric and Mechanical Properties of Muscle During Maximal and Prolonged Isokinetic Exercise
A. Nicolas (2005)
Muscle Fatigue during High-Intensity Exercise in Children
S. Ratel (2006)
Effects of Electroshock, Air Exposure, and Forced Exercise on Swim Performance in Rainbow Trout (Oncorhynchus mykiss)
C. Mitton (1994)
Reproducibility of an isokinetic eccentric muscle endurance task
J. Sauret (2009)
Contraction duration affects metabolic energy cost and fatigue in skeletal muscle.
M. Hogan (1998)
Measurement of human muscle fatigue
N. Vøllestad (1997)
Role of extracellular [Ca2+] in fatigue of isolated mammalian skeletal muscle.
S. Cairns (1998)
Rapid recovery of power output in females.
P. W. Cherry (1998)
African runners exhibit greater fatigue resistance, lower lactate accumulation, and higher oxidative enzyme activity.
A. Weston (1999)
Neuromuscular fatigue in racquet sports.
O. Girard (2009)
fatigueof hypoxia on diaphragm relaxation rate during
Augusto Campagna Torres (2015)
Development and validation of a fatigue-modified , EMG-assisted biomechanical model of the lumbar region
Omid Haddad (2011)
Contractile function is unaltered in diaphragm from mice lacking calcium release channel isoform 3.
J. S. Clancy (1999)
Determination of exponential rate constants for calpain-mediated degradation of myofibrillar complexed proteins
Tracie Albisser (1996)
Modulation by Mg2+ and ADP of ATP-sensitive potassium channels in frog skeletal muscle
C. Forestier (2004)
Supraspinal factors in human muscle fatigue: evidence for suboptimal output from the motor cortex.
S. Gandevia (1996)
Role of phosphate and calcium stores in muscle fatigue
D. Allen (2001)
Coexistence of two classes of glibenclamide-inhibitable ATP-regulated K+ channels in avian skeletal muscle
M. Fosset (2004)
The effects of intracellular injections of phosphate on intracellular calcium and force in single fibres of mouse skeletal muscle
H. Westerblad (2009)
A method for measuring sarcoplasmic reticulum calcium uptake in the skeletal muscle using Fura-2.
S. Warmington (1996)
Thérapie par l’exercice et dystrophie facio-scapulo-humérale : étude contrôlée randomisée de 6 mois d’entraînement à domicile : précédée d’une étude histologique du potentiel régénératif musculaire dans deux modèles distincts de myopathies
Sénakpon Landry Cyrille Bankolé (2014)
Effects of fatigue on sarcoplasmic reticulum and myofibrillar properties of rat single muscle fibers.
D. Danieli-Betto (2000)
force in habitual and nonhabitual caffeine consumers Caffeine potentiates low frequency skeletal muscle
C. Cupido (2015)See more