title: Multiple causes of fatigue during shortening contractions in rat slow twitch skeletal muscle.
abstract: Fatigue in muscles that shorten might have other causes than fatigue during isometric contractions, since both cross-bridge cycling and energy demand are different in the two exercise modes. While isometric contractions are extensively studied, the causes of fatigue in shortening contractions are poorly mapped. Here, we investigate fatigue mechanisms during shortening contractions in slow twitch skeletal muscle in near physiological conditions. Fatigue was induced in rat soleus muscles with maintained blood supply by in situ shortening contractions at 37°C. Muscles were stimulated repeatedly (1 s on/off at 30 Hz) for 15 min against a constant load, allowing the muscle to shorten and perform work. Fatigue and subsequent recovery was examined at 20 s, 100 s and 15 min exercise. The effects of prior exercise were investigated in a second exercise bout. Fatigue developed in three distinct phases. During the first 20 s the regulatory protein Myosin Light Chain-2 (slow isoform, MLC-2s) was rapidly dephosphorylated in parallel with reduced rate of force development and reduced shortening. In the second phase there was degradation of high-energy phosphates and accumulation of lactate, and these changes were related to slowing of muscle relengthening and relaxation, culminating at 100 s exercise. Slowing of relaxation was also associated with increased leak of calcium from the SR. During the third phase of exercise there was restoration of high-energy phosphates and elimination of lactate, and the slowing of relaxation disappeared, whereas dephosphorylation of MLC-2s and reduced shortening prevailed. Prior exercise improved relaxation parameters in a subsequent exercise bout, and we propose that this effect is a result of less accumulation of lactate due to more rapid onset of oxidative metabolism. The correlation between dephosphorylation of MLC-2s and reduced shortening was confirmed in various experimental settings, and we suggest MLC-2s as an important regulator of muscle shortening.
authors: Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway ; KG Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway.
authors: Kristin Halvorsen
authors: KH
authors: Hortemo
authors: Morten
authors: M
authors: Munkvik
authors: Per Kristian
authors: PK
authors: Lunde
authors: Ole M
authors: OM
authors: Sejersted
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D024722:Cardiac Myosins / Q000378:metabolism; D007537:Isometric Contraction / Q000502:physiology; D007773:Lactates / Q000378:metabolism; D008297:Male; D055442:Metabolome; D009119:Muscle Contraction / Q000502:physiology*; D018763:Muscle Fatigue / Q000502:physiology*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000502:physiology*; D009126:Muscle Relaxation; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors
chemical_list: D007773:Lactates; D018994:Myosin Light Chains; C107184:myosin light chain 2; D024722:Cardiac Myosins; D002118:Calcium
references: Proc Natl Acad Sci U S A. 1988 May;85(9):3265-9
references: 2966401
references: PLoS One. 2011;6(7):e22695
references: 21799933
references: J Physiol. 1989 Nov;418:327-37
references: 2621622
references: Mol Cell Biochem. 1990 May 10;94(2):113-9
references: 2374546
references: J Physiol. 2002 Feb 1;538(Pt 3):931-9
references: 11826176
references: Proc Natl Acad Sci U S A. 1990 Jan;87(1):414-8
references: 2136951
references: J Appl Physiol (1985). 1992 Nov;73(5):2105-11
references: 1474091
references: Am J Physiol Regul Integr Comp Physiol. 2009 Sep;297(3):R900-10
references: 19625691
references: Biophys J. 1985 Nov;48(5):789-98
references: 3878160
references: Pflugers Arch. 2011 Jul;462(1):143-54
references: 21347754
references: Anal Biochem. 1995 Jul 1;228(2):194-201
references: 8572295
references: J Cell Biol. 2003 Mar 17;160(6):919-28
references: 12629052
references: J Appl Physiol (1985). 1999 Apr;86(4):1101-13
references: 10194190
references: J Appl Physiol (1985). 1998 Aug;85(2):478-83
references: 9688723
references: J Appl Physiol (1985). 2010 May;108(5):1169-76
references: 20223997
references: Acta Physiol Scand. 2003 Jun;178(2):175-86
references: 12780392
references: Med Sci Sports Exerc. 2002 Dec;34(12):2091-6
references: 12471321
references: J Appl Physiol (1985). 2000 Jul;89(1):210-7
references: 10904054
references: Exp Physiol. 1995 Jul;80(4):497-527
references: 7576593
references: J Appl Physiol (1985). 2008 Jan;104(1):296-305
references: 17962573
references: J Appl Physiol (1985). 2009 Feb;106(2):378-84
references: 19057001
references: J Appl Physiol (1985). 2000 Sep;89(3):891-8
references: 10956331
references: Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2198-202
references: 18268335
references: Am J Physiol. 1984 Nov;247(5 Pt 1):C462-71
references: 6548609
references: J Mol Biol. 2006 Jan 20;355(3):432-42
references: 16325202
references: Arch Biochem Biophys. 2011 Jun 15;510(2):120-8
references: 21284933
references: J Gen Physiol. 1997 Mar;109(3):385-99
references: 9089444
references: J Appl Physiol (1985). 2005 Apr;98(4):1371-8
references: 15579570
references: Mol Cell Biochem. 2004 Apr;259(1-2):197-209
references: 15124925
references: Physiol Rev. 2008 Jan;88(1):287-332
references: 18195089
references: J Physiol. 2008 Jan 1;586(1):175-84
references: 18006575
references: J Biol Chem. 1985 Mar 25;260(6):3440-50
references: 3838314
references: J Appl Physiol (1985). 1988 Jun;64(6):2388-93
references: 3403423
references: FEBS Lett. 1995 May 1;364(1):59-62
references: 7750544
references: Philos Trans R Soc Lond B Biol Sci. 2004 Dec 29;359(1452):1829-41
references: 15647159
references: Eur J Appl Physiol. 2003 Apr;89(2):142-9
references: 12665977
references: J Physiol. 1924 May 23;58(6):373-95
references: 16993634
references: J Appl Physiol (1985). 2008 Feb;104(2):551-8
references: 18162480
references: J Physiol. 1977 Nov;272(3):769-78
references: 592214
references: Am J Physiol. 1986 Apr;250(4 Pt 1):C657-60
references: 3754389
references: J Biol Chem. 2013 May 10;288(19):13446-54
references: 23530050
references: J Biol Chem. 1999 Jul 23;274(30):21085-94
references: 10409661
references: Muscle Nerve. 2007 Dec;36(6):756-77
references: 17823954
references: Sports Med. 1985 Mar-Apr;2(2):120-32
references: 3847097
references: Anal Biochem. 1990 Dec;191(2):321-31
references: 2150742
references: Am J Physiol. 1993 Mar;264(3 Pt 1):C577-82
references: 8460665