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Determinants of surface membrane and transverse-tubular excitability in skeletal muscle: implications for high-intensity exercise

  • Michael I. Lindinger (a1)
Abstract

The fatigue of high-intensity exercise is now believed to reside primarily within the excitation–contraction coupling processes associated with the plasma membrane of skeletal muscle (sarcolemm) and calcium-mediated events leading to myofilament sliding. This paper summarizes recent developments and advances in the identification of factors that contribute to changes in sarcolemmal excitability of mammalian skeletal muscle as a consequence of high-intensity exercise. There is an increasing recognition of the probable role that is played by the transverse tubular system (T-system), a system that comprises c. 80% of the total sarcolemmal surface capable of ion exchange. Furthermore, the fluid within the T-system has limited access to interstitial fluid bathing myofibres; hence, T-system fluid is probably markedly different from interstitial fluid during high-intensity exercise. Mechanically skinned fibre preparation is providing many new insights into functions of the surface membrane and T-system in fatigue. A scenario is developed whereby accumulation of potassium within the T-system ([K+]o) contributes to reduced membrane excitability, as well as lowering of T-system sodium and chloride, concomitant with loss of intracellular potassium ([K+]i) and accumulation of intracellular sodium ([Na+]) and chloride ([Cl]). Lowering the [Na+]o/[Na+]i ratio and raising myoplasmic [Na+]i have been shown to decrease membrane excitability and impair action potential propagation. Maintained high [Cl]o may also have a protective effect in maintaining membrane excitability, and this effect appears to be very pronounced in the presence of raised [K+]o. In contrast to dogma associating high [H+] to fatigue, recent studies have also shown that induced acidosis that results in increased [H+]o and [H+]i restores force production in muscles and skinned fibres fatigued by intermittent tetanic stimulation. This effect may be due to a decrease in surface membrane Cl permeability that serves to restore membrane excitability. During high-intensity exercise, simultaneous changes in trans-membrane ion concentrations and membrane ion conductances may serve to reduce impairment of membrane excitability that provides for a maintained, though reduced, contractile function.

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1Lamb, GD (1995). Excitation–contraction coupling and fatigue mechanisms in skeletal muscle: studies with mechanically skinned fibres. Journal of Muscle Research and Cell Motility 23: 8191.
2Nielsen, OB, Ørtenblad, N, Lamb, GD and Stephenson, DG (2004). Excitability of the T-tubular system in rat skeletal muscle: roles of K + and Na + gradients and Na + –K + pump activity. Journal of Physiology 557: 133146.
3Sejersted, OM and Sjogaard, G (2000). Dynamics and consequences of potassium shifts in skeletal muscle and heart during exercise. Physiological Reviews 80: 14111481.
4Renaud, JM (2002). Modulation of force development by Na +, K +, Na + –K + pump and K ATP channel. Canadian Journal of Applied Physiology 27: 296315.
5Gosmanov, AR, Lindinger, MI and Thomason, DB (2003). Riding the tides: [K + ] and volume regulation by Muscle Na + –K + –2Cl - cotransport activity. News in Physiological Sciences 18: 196200.
6Clausen, T (2003). Na +, K + pump regulation and skeletal muscle contractility. Physiological Reviews 83: 12691324.
7Green, HJ (2004). Membrane excitability, weakness, and fatigue. Canadian Journal of Applied Physiology 29: 291307.
8Yonemura, K (1967). Resting and action potentials in red and white muscle of the rat. Japanese Journal of Physiology 17: 708719.
9Elliot, GF (1973). Donan and osmotic effects in muscle fibres without membranes. Journal of Mechanochemistry and Cell Motility 2: 8389.
10Abe, H (2000). Role of histidine-related compounds as intracellular proton buffering constituents in vertebrate muscle. Biochemistry (Moscow) 65: 757765.
11Beam, KG, Caldwell, JH and Campbell, DT (1985). Na channels in skeletal muscle concentrated near the neuromuscular junction. Nature 313: 588590.
12Jacquemond, V and Allard, B (1998). Activation of Ca 2+ -activated K + channels by an increase in intracellular Ca 2+ induced by depolarization of mouse skeletal muscle fibres. Journal of Physiology 509: 93102.
13Rios, E and Pizarro, G (1991). Voltage sensor of excitation–contraction coupling in skeletal muscle. Physiological Reviews 71: 849908.
14Rios, E, Pizarro, G and Stefani, E (1992). Charge movement and the nature of signal transduction in skeletal muscle excitation–contraction coupling. Annual Reviews of Physiology 54: 109133.
15Nielsen, JJ, Kristensen, M, Hellsten, Y, Bangsbo, J and Juel, C (2003). Localization and function of ATP-sensitive potassium channels in human skeletal muscle. American Journal of Physiology 284: R558R563
16Cairns, SP, Buller, SJ, Loiselle, DS and Renaud, JM (2003). Changes of action potentials and force at lowered [Na + ] o in mouse skeletal muscle: implications for fatigue. American Journal of Physiology 285: C1131C1141
17Klocke, R, Steinmeyer, K, Jentsch, TJ and Jockusch, H (1994). Role of innervation, excitability, and myogenic factors in the expression of the muscular chloride channel CIC-1. Journal of Biological Chemistry 269: 2763527639.
18Lindinger, MI, Hawke, TJ, Vickery, L, Bradford, L and Lipskie, SL (2001). An integrative, in situ approach to examining K + flux in resting skeletal muscle. Canadian Journal of Physiology and Pharmacology 79: 9961006.
19Maughan, D and Recchia, C (1985). Diffusible sodium, potassium, magnesium, calcium and phosphorus in frog skeletal muscle. Journal of Physiology 368: 545563.
20Bretag, AH (1987). Muscle chloride channels. Physiological Reviews 67: 618724.
21Lindinger, MI and Heigenhauser, GJF (1991). The roles of ion fluxes in skeletal muscle fatigue. Canadian Journal of Physiology and Pharmacology 69: 246253.
22Sen, CK, Hanninen, O and Orlov, SN (1995). Unidirectional sodium and potassium flux in myogenic L6 cells: mechanisms and volume-dependent regulation. Journal of Applied Physiology 78: 272281.
23Lang, F, Busch, GL, Ritter, M, Volkl, H, Waldegger, S, Gulbins, E and Haussinger, D (1998). Functional significance of cell volume regulatory mechanisms. Physiological Reviews 78: 247306.
24Lindinger, MI and Heigenhauser, GJF (1988). Ion fluxes during tetanic stimulation in the isolated perfused rat hindlimb. American Journal of Physiology 254: R117R126.
25Metzger, JM and Fitts, RH (1986). Fatigue from high and low frequency stimulation: role of sarcolemma action potentials. Experimental Neurology 93: 320333.
26Cairns, SP, Flatman, JA and Clausen, T (1995). Relation between extracellular [K + ], membrane potential and contraction in rat soleus muscle: modulation by the Na + –K + pump. Pflugers Archivs 430: 909915.
27Korge, P and Campbell, KB (1995). The importance of ATPase microenvironment in muscle fatigue: a hypothesis. International Journal of Sports Medicine and Physiological Biochemistry 16: 172179.
28Tricarico, D, Mallamaci, R, Barbieri, M and Conte-Camerino, D (1997). Modulation of ATP-sensitive K + channel by insulin in rat skeletal muscle fibres. Biochemistry and Biophysics Research Communications 232: 536539.
29Weiss, JN and Lamp, ST (1989). Cardiac ATP-sensitive K + channels. Evidence for preferential regulation by glycolysis. Journal of General Physiology 94: 911935.
30James, JH, Wagner, KR, King, J, Leffler, RE, Upputuri, RK, Balasubramaniam, A, Friend, LA, Shelly, DAPRJ and Fisher, JE (1999). Stimulation of both aerobic glycolysis and Na + –K + –ATPase activity in skeletal muscle by epinephrine or amylin. American Journal of Physiology 277: E176E186
31Semb, SO and Sejersted, OM (1996). Fuzzy space and control of Na +, K + -pump rate in heart and skeletal muscle. Acta Physiologica Scandinavica 156: 213225.
32Silverman, BZ, Warley, A, Miller, JIA, James, AF and Shattock, MJ (2003). Is there a transient rise in sub-sarcolemmal Na and activation of Na/K pump current following activation of I Na in ventricular myocardium? Cardiovascular Research 57: 10251034.
33Lindinger, MI, Hawke, TJ, Lipskie, SL, Schaefer, HD and Vickery, L (2002). K + transport and volume regulatory response by NKCC in resting rat hindlimb skeletal muscle. Cellular Physiology and Biochemistry 12: 279292.
34Franzini-Armstrong, C and Jorgensen, AO (1994). Structure and development of E–C coupling units in skeletal muscle. Annual Reviews of Physiology 56: 509534.
35Launikonis, BS and Stephenson, DG (2002). Properties of the vertebrate skeletal muscle tubular system as a sealed compartment. Cell Biology International 26: 921929.
36Soeller, C and Cannell, MB (1999). Examination of the transverse tubular system in living rat myocytes by 2-photon microscopy and digital image-processing techniques. Circulation Research 84: 266275.
37Launikonis, BS and Stephenson, DG (2004). Osmotic properties of the sealed tubular system of tad and rat skeletal muscle. Journal of General Physiology 123: 231247.
38Sjogaard, G (1991). Role of exercise-induced potassium fluxes underlying muscle fatigue: a brief review. Canadian Journal of Physiology and Pharmacology 69: 238245.
39Dulhunty, AF (1979). Distribution of potassium and chloride permeability over the surface and T-tubule membranes of mammalian skeletal muscle. Journal of Membrane Biology 45: 293310.
40Renaud, JM and Light, P (1992). Effects of K + on the twitch and tetanic contraction in the sartorius muscle of the frog, Rana pipiens. Implication for fatigue in vivo. Canadian Journal of Physiology and Pharmacology 70: 12361246.
41Ruff, RL (1997). Sodium channel regulation of skeletal muscle membrane excitability. Annals of the New York Academy of Sciences 835: 6476.
42Clark, RB, Tremblay, A, Melnyk, P, Allen, BG, Giles, WR and Fiset, C (2001). T-tubule localization of the inward-rectifier K + channel in mouse ventricular myocytes: a role in K + accumulation. Journal of Physiology 537: 979992.
43Mohr, M, Nordsberg, N, Nielsen, JJ, Pedersen, LD, Fischer, C, Krustrup, P and Bangsbo, J (2004). Potassium kinetics in human muscle interstitium during repeated intense exercise in relation to fatigue. Pflugers Archivs 448: 452456.
44Hnik, P, Holas, M, Krekule, I, Kriz, N, Mejsnar, J, Smiesko, V, Ujec, E and Vyskocil, F (1976). Work-induced potassium changes in skeletal muscle and effluent venous blood assessed by liquid ion-exchanger microelectrodes. Pflugers Archivs 362: 8594.
45Vyskocil, F, Hnik, P, Rehfeldt, H, Vejsada, R and Ujec, E (1983). The measurement of K + e concentration changes in human skeletal muscles during volitional contractions. Pflugers Archivs 399: 235237.
46Cairns, SP, Hing, WA, Slack, JR, Mills, RG and Loiselle, DS (1997). Different effects of raised [K + ] o on membrane potential and contraction in mouse fast- and slow-twitch muscle. American Journal of Physiology 273: C598C611.
47Gonzalez-Serratos, H, Somlyo, AV, McClellan, G, Shuman, H, Borrero, LM and Somlyo, AP (1978). Composition of vacuoles and sarcoplasmic reticulum in fatigued muscle: electron probe analysis. Proceedings of the National Academy of Sciences 75: 13291333.
48Sembrowich, WL, Johnson, D, Wang, E and Hutchison, TE (1982). Electron microprobe analysis of fatigued fast- and slow-twitch muscle. In: Knuttgen, HG, Vogel, JA & Poort-mans, J (eds), Biochemistry of Exercise. Champaign, IL: Human Kinetics Vol. 13 pp. 571576.
49Cairns, SP, Dulhunty, AF and Renaud, JM (1995). High-frequency fatigue in rat skeletal muscle: role of extracellular ion concentrations. Muscle & Nerve 18: 890898.
50Posterino, GS, Lamb, GD and Stephensen, DG (2000). Twitch and tetanic force responses and longitudinal propagation of action potentials in skinned skeletal muscle fibres of the rat. Journal of Physiology 527: 131137.
51Nielsen, OB, de Paoli, F and Overgaard, K (2001). Protective effects of lactic acid on force production in rat skeletal muscle. Journal of Physiology 536: 161166.
52Renaud, JM and Mainwood, GW (1985). The interactive effects of fatigue and pH on the ionic conductance of frog sartorius muscle fibres. Canadian Journal of Physiology and Pharmacology 63: 14441453.
53Fink, R and Luttgau, HC (1976). An evaluation of the membrane constants and the potassium conductance in metabolically exhausted muscle fibres. Journal of Physiology 263: 215238.
54Coonan, JR and Lamb, GD (1998). Effect of transverse-tubular chloride conductance on excitability in skinned skeletal muscle fibres of rat and toad. Journal of Physiology 509: 551564.
55Pedersen, TH, Nielsen, OB, Lamb, GD and Stephensen, DG (2004). Intracellular acidosis enhances the excitability of working muscle. Science 305: 11441147.
56Pedersen, TH, de Paoli, T and Nielsen, OB (2005). Increased excitability of acidified skeletal muscle: role of chloride conductance. Journal of General Physiology 125: 237246.
57Fahlke, C, Durr, C and George, AL Jr (1997). Mechanism of ion permeation in skeletal muscle chloride channels. Journal of General Physiology 110: 551564.
58Lehmann-Horn, F and Jurkat-Rott, K (1999). Voltage-gated ion channels and hereditary disease. Physiological Reviews 79: 13171372.
59Gurnett, CA, Kahl, SD, Anderson, RD and Campbell, KP (1995). Absence of skeletal muscle sarcolemma chloride channel CIC-1 in myotonic mice. Journal of Biological Chemistry 270: 90359038.
60Milton, RL and Behforouz, MA (1995). Na channel density in extrajunctional sarcolemma of fast and slow twitch mouse skeletal muscle fibres: functional implications and plasticity after fast motoneuron transplantation on to a slow muscle. Journal of Muscle Research and Cell Motility 16: 430439.
61Cairns, SP, Ruzhynsky, V and Renaud, JM (2004). Protective role of extracellular chloride in fatigue of isolated mammalian skeletal muscle. American Journal of Physiology 287: C762C770
62van Emst, MG, Klarenbeek, S, Schot, A, Plomp, JJ, Doornenbal, A and Everts, ME (2004). Reducing chloride conductance prevents hyperkalaemia-induced loss of twitch force in rat slow-twitch muscle. Journal of Physiology 561: 169181.
63Gosmanov, AR, Nordvedt, NC, Brown, R and Thomson, DB (2002). Exercise effects on muscle beta-adrenergic signalling for MAPK-dependent NKCC activity are rapid and persistent. Journal of Applied Physiology 93: 14571465.
64Lundvall, J, Mellander, S, Westling, H and White, T (1972). Fluid transfer between blood and tissues during exercise. Acta Physiologica Scandinavica 85: 258269.
65Bergstrom, J and Hultman, E (1966). The effect of exercise on muscle glycogen and electrolytes in normals. Scandinavian Journal of Clinical and Laboratory Investigation 18: 15.
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Equine and Comparative Exercise Physiology
  • ISSN: 1478-0615
  • EISSN: 1479-070X
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