Abstract
A progressive reduction in muscle fiber conduction velocity is typically observed during fatiguing muscle contraction. Although the exact causes of the conduction velocity decrease have not yet been fully established, increasing evidence suggests that changes in extracellular potassium concentration may be largely responsible. In this study, a mathematical model was developed to examine the effect of extracellular potassium concentration on the muscle fiber action potential and conduction velocity. The model was used to simulate changes in extracellular potassium concentration at a range of temperatures and extracellular potassium accumulation during repetitive stimulation of the muscle fiber at 37 °C. The action potential broadened, and its amplitude and conduction velocity decreased as extracellular potassium concentration increased. The potassium-induced changes in action potential shape and conduction velocity were eliminated when the inward rectifier channels were removed from the model. The results support the hypothesis that accumulation of extracellular potassium ions may be a major contributor to the reduction in muscle fiber conduction velocity and loss of membrane excitability during fatiguing contractions. They additionally suggest that inward rectifier currents play a critical role in potassium-induced membrane depolarization, leading to increased sodium inactivation and resulting in the observed reduction in conduction velocity and membrane excitability.
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Adrian, R. H. The effect of internal and external potassium concentration on the membrane potential of frog muscle. J. Physiol. 133(3):631–658, 1956.
Adrian, R. H., and L. D. Peachey. Reconstruction of the action potential of frog sartorius muscle. J. Physiol. 235(1):103–131, 1973.
Bigland-Ritchie, B., E. Cafarelli, and N. K. Vollestad. Fatigue of submaximal static contractions. Acta Physiol. Scand. Suppl. 556:137–148, 1986.
Bigland-Ritchie, B., et al. Muscle temperature, contractile speed, and motoneuron firing rates during human voluntary contractions. J. Appl. Physiol. 73(6):2457–2461, 1992.
Bouchard, R., et al. Changes in extracellular K+ concentration modulate contractility of rat and rabbit cardiac myocytes via the inward rectifier K+ current IK1. J. Physiol. 556(3):773–790, 2004.
Bretag, A. H. Muscle chloride channels. Physiol. Rev. 67(2):618–724, 1987.
Brody, L. R., et al. pH-induced effects on median frequency and conduction velocity of the myoelectric signal. J. Appl. Physiol. 71(5):1878–1885, 1991.
Caffier, G., and N. E. Shvinka. Effect of temperature on the inward rectifier and gramicidin A-induced channels in the membrane of frog skeletal muscle fibres. Gen. Physiol. Biophys. 5(1):47–51, 1986.
Cannon, S. C., R. H. Brown, Jr., and D. P. Corey. Theoretical reconstruction of myotonia and paralysis caused by incomplete inactivation of sodium channels. Biophys. J. 65(1):270–288, 1993.
Clausen, T. Na+–K+ pump regulation and skeletal muscle contractility. Physiol. Rev. 83(4):1269–1324, 2003.
Dal Santo, G. A Laboratory Basis for Anesthesiology. Padua: PICCIN, 1993, 900 pp.
De Luca, C. J. Myoelectrical manifestations of localized muscular fatigue in humans. Crit. Rev. Biomed. Eng. 11(4):251–279, 1984.
Debold, E. P., H. Dave, and R. H. Fitts. Fiber type and temperature dependence of inorganic phosphate: implications for fatigue. Am. J. Physiol. Cell Physiol. 287(3):C673–C681, 2004.
Fabiato, A., and F. Fabiato. Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiace and skeletal muscles. J. Physiol. 276:233–255, 1978.
Farina, D., and R. Merletti. Methods for estimating muscle fibre conduction velocity from surface electromyographic signals. Med. Biol. Eng. Comput. 42(4):432–445, 2004.
Hayward, L. J., et al. Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness. J. Clin. Invest. 118(4):1437–1449, 2008.
Henneberg, K. A., and F. A. Roberge. Simulation of propagation along an isolated skeletal muscle fiber in an isotropic volume conductor. Ann. Biomed. Eng. 25(1):5–28, 1997.
Hodgkin, A. L., and A. F. Huxley. A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. 117(4):500–544, 1952.
Hodgkin, A. L., and B. Katz. The effect of sodium ions on the electrical activity of giant axon of the squid. J. Physiol. 108(1):37–77, 1949.
Hodgkin, A. L., and S. Nakajima. The effect of diameter on the electrical constants of frog skeletal muscle fibres. J. Physiol. 221(1):105–120, 1972.
Jones, D. A. Muscle Fatigue Due to Changes Beyond the Neuromuscular Junction. London: Pitman Medical, pp. 178–196, 1981.
Juel, C. Muscle action potential propagation velocity changes during activity. Muscle Nerve 11(7):714–719, 1988.
Juel, C. Na+–K+-ATPase in rat skeletal muscle: muscle fiber-specific differences in exercise-induced changes in ion affinity and maximal activity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296(1):R125–R132, 2009.
Juel, C., et al. Interstitial K(+) in human skeletal muscle during and after dynamic graded exercise determined by microdialysis. Am. J. Physiol. Regul. Integr. Comp. Physiol. 278(2):R400–R406, 2000.
Kirsch, G. E., R. A. Nichols, and S. Nakajima. Delayed rectification in the transverse tubules: origin of the late after-potential in frog skeletal muscle. J. Gen. Physiol. 70(1):1–21, 1977.
Kossler, F., et al. External potassium and action potential propagation in rat fast and slow twitch muscles. Gen. Physiol. Biophys. 10(5):485–498, 1991.
Kristensen, M., T. Hansen, and C. Juel. Membrane proteins involved in potassium shifts during muscle activity and fatigue. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290(3):R766–R772, 2006.
Lannergren, J., and H. Westerblad. Force and membrane potential during and after fatiguing, continuous high-frequency stimulation of single Xenopus muscle fibres. Acta Physiol. Scand. 128(3):359–368, 1986.
Li, J., et al. Interstitial K+ concentration in active muscle after myocardial infarction. Am J Physiol Heart Circ Physiol. 292(2):H808–H813, 2007.
Lindstrom, L., and R. Magnusson. Interpretation of myoelectric power spectra: a model and its applications. Proc. IEEE 65(5):653–662, 1977.
Lindstrom, L., R. Magnusson, and I. Petersen. Muscular fatigue and action potential conduction velocity changes studied with frequency analysis of EMG signals. Electromyography 10(4):341–356, 1970.
Ling, G., and R. W. Gerard. External potassium and the membrane potential of single muscle fibers. Nature 165(4186):113, 1950.
Lowery, M., P. Nolan, and M. O’Malley. Electromyogram median frequency, spectral compression and muscle fibre conduction velocity during sustained sub-maximal contraction of the brachioradialis muscle. J. Electromyogr. Kinesiol. 12(2):111–118, 2002.
Luo, C. H., and Y. Rudy. A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. Circ. Res. 74(6):1071–1096, 1994.
Masuda, K., et al. Changes in surface EMG parameters during static and dynamic fatiguing contractions. J. Electromyogr. Kinesiol. 9(1):39–46, 1999.
McComas, A. J., et al. The role of the Na+, K+-pump in delaying muscle fatigue. In: Neuromuscular Fatigue, edited by A. J. Sargeant and D. Kernell. Amsterdam: Royal Netherlands Academy of Arts & Sciences, 1993, pp. 35–43.
McKenna, M. J. The roles of ionic processes in muscular fatigue during intense exercise. Sports Med. 13(2):134–145, 1992.
McKenna, M. J., J. Bangsbo, and J. M. Renaud. Muscle K+, Na+, and Cl disturbances and Na+–K+ pump inactivation: implications for fatigue. J. Appl. Physiol. 104(1):288–295, 2008.
Merletti, R., M. Knaflitz, and C. J. De Luca. Myoelectric manifestations of fatigue in voluntary and electrically elicited contractions. J. Appl. Physiol. 69(5):1810–1820, 1990.
Mills, K. R., and R. H. Edwards. Muscle fatigue in myophosphorylase deficiency: power spectral analysis of the electromyogram. Electroencephalogr. Clin. Neurophysiol. 57(4):330–335, 1984.
Mortimer, J. T., R. Magnusson, and I. Petersen. Conduction velocity in ischemic muscle: effect on EMG frequency spectrum. Am. J. Physiol. 219(5):1324–1329, 1970.
Nielsen, J. J., et al. Effects of high-intensity intermittent training on potassium kinetics and performance in human skeletal muscle. J. Physiol. 554(3):857–870, 2004.
Nielsen, O. B., et al. Excitability of the T-tubular system in rat skeletal muscle: roles of K+ and Na+ gradients and Na+–K+ pump activity. J. Physiol. 557(Pt 1):133–146, 2004.
Nordsborg, N., et al. Muscle interstitial potassium kinetics during intense exhaustive exercise: effect of previous arm exercise. Am. J. Physiol. Regul. Integr. Comp. Physiol. 285(1):R143–R148, 2003.
Overgaard, K., O. B. Nielsen, and T. Clausen. Effects of reduced electrochemical Na+ gradient on contractility in skeletal muscle: role of the Na+–K+ pump. Pflugers Arch. 434(4):457–465, 1997.
Pappone, P. A. Voltage-clamp experiments in normal and denervated mammalian skeletal muscle fibres. J. Physiol. 306:377–410, 1980.
Pedersen, T. H., et al. Intracellular acidosis enhances the excitability of working muscle. Science 305(5687):1144–1147, 2004.
Ruff, R. L., L. Simoncini, and W. Stuhmer. Slow sodium channel inactivation in mammalian muscle: a possible role in regulating excitability. Muscle Nerve 11(5):502–510, 1988.
Rutkove, S. B. Effects of temperature on neuromuscular electrophysiology. Muscle Nerve 24(7):867–882, 2001.
Sejersted, O. M., and G. Sjogaard. Dynamics and consequences of potassium shifts in skeletal muscle and heart during exercise. Physiol. Rev. 80(4):1411–1481, 2000.
Sjogaard, G. Potassium and fatigue: the pros and cons. Acta Physiol. Scand. 156(3):257–264, 1996.
Sjogaard, G., G. Savard, and C. Juel. Muscle blood flow during isometric activity and its relation to muscle fatigue. Eur. J. Appl. Physiol. Occup. Physiol. 57(3):327–335, 1988.
Standen, N. B., and P. R. Stanfield. Inward rectification in skeletal muscle: a blocking particle model. Pflugers Arch. 378(2):173–176, 1978.
Stefani, E., and A. B. Steinbach. Resting potential and electrical properties of frog slow muscle fibres. Effect of different external solutions. J. Physiol. 203(2):383–401, 1969.
Stephanova, D. I., and G. V. Dimitrov. Mathematical modeling of ionic processes in human skeletal muscle fibres. Electromyogr. Clin. Neurophysiol. 22(5):329–347, 1982.
Stulen, F. B., and C. J. DeLuca. Frequency parameters of the myoelectric signal as a measure of muscle conduction velocity. IEEE Trans. Biomed. Eng. 28(7):515–523, 1981.
Venosa, R. A., and P. Horowicz. Density and apparent location of the sodium pump in frog sartorius muscle. J. Membr. Biol. 59(3):225–232, 1981.
Vyskocil, F., et al. The measurement of K+e concentration changes in human muscles during volitional contractions. Pflugers Arch. 399(3):235–237, 1983.
Wallinga, W., et al. Modelling action potentials and membrane currents of mammalian skeletal muscle fibres in coherence with potassium concentration changes in the T-tubular system. Eur. Biophys. J. 28(4):317–329, 1999.
Westerblad, H., D. G. Allen, and J. Lannergren. Muscle fatigue: lactic acid or inorganic phosphate the major cause? News Physiol. Sci. 17:17–21, 2002.
Whalley, D. W., et al. Voltage-independent effects of extracellular K+ on the Na+ current and phase 0 of the action potential in isolated cardiac myocytes. Circ. Res. 75(3):491–502, 1994.
Zwarts, M. J., and L. Arendt-Nielsen. The influence of force and circulation on average muscle fibre conduction velocity during local muscle fatigue. Eur. J. Appl. Physiol. Occup. Physiol. 58(3):278–283, 1988.
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Fortune, E., Lowery, M.M. Effect of Extracellular Potassium Accumulation on Muscle Fiber Conduction Velocity: A Simulation Study. Ann Biomed Eng 37, 2105–2117 (2009). https://doi.org/10.1007/s10439-009-9756-4
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DOI: https://doi.org/10.1007/s10439-009-9756-4