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Physiol. Rev. 74: 49-94, 1994;
0031-9333/94 $15.00
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Physiological Reviews, Vol 74, 49-94, Copyright © 1994 by American Physiological Society

JOURNAL ARTICLE

Cellular mechanisms of muscle fatigue

R. H. Fitts
Department of Biology, Marquette University, Milwaukee, Wisconsin.

Fatigue, defined as the failure to maintain the required or expected power output, is a complex problem, since multiple factors are clearly involved, with the relative importance of each dependent on the fiber type composition of the contracting muscles(s), and the intensity, type, and duration of the contractile activity. The primary sites of fatigue appear to be within the muscle cell itself and for the most part do not involve the central nervous system or the neuromuscular junction. The major hypotheses of fatigue center on disturbances in the surface membrane, E-C coupling, or metabolic events. The cell sites most frequently linked to the etiology of skeletal muscle fatigue are shown in Figure 1. Skeletal muscles are composed of at least four distinct fiber types (3 fast twitch and 1 slow twitch), with the slow type I and fast type IIa fibers containing the highest mitochondrial content and fatigue resistance. Despite fiber type differences in the degree of fatigability, the contractile properties undergo characteristic changes with the development of fatigue that can be observed in whole muscles, single motor units, and single fibers. The Po declines, and the contraction and relaxation times are prolonged. Additionally, there is a decrease in the peak rate of tension development and decline and a reduced Vo. Changes in Vo are more resistant to fatigue than Po and are not observed until Po has declined by at least 10% of its initial prefatigued value. However, the reduced peak power by which fatigue is defined results from both a reduction in Vo and Po. In the absence of muscle fiber damage, the prolonged relaxation time associated with fatigue causes the force-frequency curve to shift to the left, such that peak tensions are obtained at lower frequencies of stimulation. In a mechanism not clearly understood, the central nervous system senses this condition and reduces the alpha-motor nerve activation frequency as fatigue develops. In some cases, selective LFF develops that displaces the force-frequency curve to the right. Although not proven, it appears likely that this condition is associated with and likely caused by muscle injury, such that the SR releases less Ca2+ at low frequencies of activation. Alternatively, LFF could result from a reduced membrane excitability, such that the sarcolemma action potential frequency is considerably less than the stimulation frequency.(ABSTRACT TRUNCATED AT 400 WORDS)


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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. D. Sandiford, H. J. Green, T. A. Duhamel, J. D. Schertzer, J. D. Perco, and J. Ouyang
Muscle Na-K-pump and fatigue responses to progressive exercise in normoxia and hypoxia
Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2005; 289(2): R441 - R449.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
D. Street, J.-J. Nielsen, J. Bangsbo, and C. Juel
Metabolic alkalosis reduces exercise-induced acidosis and potassium accumulation in human skeletal muscle interstitium
J. Physiol., July 15, 2005; 566(2): 481 - 489.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
C. M. Stary and M. C. Hogan
Intracellular pH during sequential, fatiguing contractile periods in isolated single Xenopus skeletal muscle fibers
J Appl Physiol, July 1, 2005; 99(1): 308 - 312.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
A. K. Hansen, T. Clausen, and O. B. Nielsen
Effects of lactic acid and catecholamines on contractility in fast-twitch muscles exposed to hyperkalemia
Am J Physiol Cell Physiol, July 1, 2005; 289(1): C104 - C112.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
H. E. Kan, T. E. Buse-Pot, R. Peco, D. Isbrandt, A. Heerschap, and A. de Haan
Lower force and impaired performance during high-intensity electrical stimulation in skeletal muscle of GAMT-deficient knockout mice
Am J Physiol Cell Physiol, July 1, 2005; 289(1): C113 - C119.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
C. R. Hancock, E. Janssen, and R. L. Terjung
Skeletal muscle contractile performance and ADP accumulation in adenylate kinase-deficient mice
Am J Physiol Cell Physiol, June 1, 2005; 288(6): C1287 - C1297.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
D. Danieli-Betto, E. Germinario, A. Esposito, A. Megighian, M. Midrio, B. Ravara, E. Damiani, L. D. Libera, R. A. Sabbadini, and R. Betto
Sphingosine 1-phosphate protects mouse extensor digitorum longus skeletal muscle during fatigue
Am J Physiol Cell Physiol, June 1, 2005; 288(6): C1367 - C1373.
[Abstract] [Full Text] [PDF]

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 Br. J. Sports. Med.Home page
J-M Vallier, F Grego, F Basset, R Lepers, T Bernard, and J Brisswalter
Effect of fluid ingestion on neuromuscular function during prolonged cycling exercise
Br. J. Sports Med., April 1, 2005; 39(4): e17 - e17.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
T. R Moopanar and D. G Allen
Reactive oxygen species reduce myofibrillar Ca2+ sensitivity in fatiguing mouse skeletal muscle at 37{degrees}C
J. Physiol., April 1, 2005; 564(1): 189 - 199.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
M. I Lindinger
Intracellular [H+]: a determinant of cell volume in skeletal muscle
J. Physiol., March 15, 2005; 563(3): 643 - 643.
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 J. Physiol.Home page
G. Todd, J. E Butler, J. L Taylor, and S. C Gandevia
Hyperthermia: a failure of the motor cortex and the muscle
J. Physiol., March 1, 2005; 563(2): 621 - 631.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
L. Nybo, M. K Dalsgaard, A. Steensberg, K. Moller, and N. H Secher
Cerebral ammonia uptake and accumulation during prolonged exercise in humans
J. Physiol., February 15, 2005; 563(1): 285 - 290.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
C. A. Kindig, R. A. Howlett, C. M. Stary, B. Walsh, and M. C. Hogan
Effects of acute creatine kinase inhibition on metabolism and tension development in isolated single myocytes
J Appl Physiol, February 1, 2005; 98(2): 541 - 549.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
D. P Gitterman, J Wilson, and A. D Randall
Functional properties and pharmacological inhibition of ASIC channels in the human SJ-RH30 skeletal muscle cell line
J. Physiol., February 1, 2005; 562(3): 759 - 769.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
P. A. Roberts, S. J. G. Loxham, S. M. Poucher, D. Constantin-Teodosiu, and P. L. Greenhaff
Acetyl-CoA provision and the acetyl group deficit at the onset of contraction in ischemic canine skeletal muscle
Am J Physiol Endocrinol Metab, February 1, 2005; 288(2): E327 - E334.
[Abstract] [Full Text] [PDF]

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 JGPHome page
T. H. Pedersen, F. de Paoli, and O. B. Nielsen
Increased Excitability of Acidified Skeletal Muscle: Role of Chloride Conductance
J. Gen. Physiol., January 31, 2005; 125(2): 237 - 246.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
M. Kristensen, J. Albertsen, M. Rentsch, and C. Juel
Lactate and force production in skeletal muscle
J. Physiol., January 15, 2005; 562(2): 521 - 526.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
H. J. Green, T. A. Duhamel, S. Ferth, G. P. Holloway, M. M. Thomas, A. R. Tupling, S. M. Rich, and J. E. Yau
Reversal of muscle fatigue during 16 h of heavy intermittent cycle exercise
J Appl Physiol, December 1, 2004; 97(6): 2166 - 2175.
[Abstract] [Full Text] [PDF]

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 Br. J. Sports. Med.Home page
A St Clair Gibson and T D Noakes
Evidence for complex system integration and dynamic neural regulation of skeletal muscle recruitment during exercise in humans
Br. J. Sports Med., December 1, 2004; 38(6): 797 - 806.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
T. L Dutka and G. D Lamb
Effect of low cytoplasmic [ATP] on excitation-contraction coupling in fast-twitch muscle fibres of the rat
J. Physiol., October 15, 2004; 560(2): 451 - 468.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
J. A. Leppik, R. J. Aughey, I. Medved, I. Fairweather, M. F. Carey, and M. J. McKenna
Prolonged exercise to fatigue in humans impairs skeletal muscle Na+-K+-ATPase activity, sarcoplasmic reticulum Ca2+ release, and Ca2+ uptake
J Appl Physiol, October 1, 2004; 97(4): 1414 - 1423.
[Abstract] [Full Text] [PDF]

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 Br. J. Sports. Med.Home page
T D Noakes and A St Clair Gibson
Logical limitations to the "catastrophe" models of fatigue during exercise in humans
Br. J. Sports Med., October 1, 2004; 38(5): 648 - 649.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
P. Connes, D. Bouix, G. Py, C. Caillaud, P. Kippelen, J.-F. Brun, A. Varray, C. Prefaut, and J. Mercier
Does exercise-induced hypoxemia modify lactate influx into erythrocytes and hemorheological parameters in athletes?
J Appl Physiol, September 1, 2004; 97(3): 1053 - 1058.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
E. P. Debold, H. Dave, and R. H. Fitts
Fiber type and temperature dependence of inorganic phosphate: implications for fatigue
Am J Physiol Cell Physiol, September 1, 2004; 287(3): C673 - C681.
[Abstract] [Full Text] [PDF]

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 Exp PhysiolHome page
C. M. Stary, O. Mathieu-Costello, and M. C. Hogan
Resistance to fatigue of individual Xenopus single skeletal muscle fibres is correlated with mitochondrial volume density
Exp Physiol, September 1, 2004; 89(5): 617 - 621.
[Abstract] [Full Text] [PDF]

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 ScienceHome page
T. H. Pedersen, O. B. Nielsen, G. D. Lamb, and D. G. Stephenson
Intracellular Acidosis Enhances the Excitability of Working Muscle
Science, August 20, 2004; 305(5687): 1144 - 1147.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
U. R. Mikkelsen, A. Fredsted, H. Gissel, and T. Clausen
Excitation-induced Ca2+ influx and muscle damage in the rat: loss of membrane integrity and impaired force recovery
J. Physiol., August 15, 2004; 559(1): 271 - 285.
[Abstract] [Full Text] [PDF]


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