title: Low force contractions induce fatigue consistent with muscle mRNA expression in people with spinal cord injury.
abstract: Spinal cord injury (SCI) is associated with muscle atrophy, transformation of muscle fibers to a fast fatigable phenotype, metabolic inflexibility (diabetes), and neurogenic osteoporosis. Electrical stimulation of paralyzed muscle may mitigate muscle metabolic abnormalities after SCI, but there is a risk for a fracture to the osteoporotic skeletal system. The goal of this study was to determine if low force stimulation (3 Hz) causes fatigue of chronically paralyzed muscle consistent with selected muscle gene expression profiles. We tested 29 subjects, nine with a SCI and 20 without and SCI, during low force fatigue protocol. Three SCI and three non-SCI subjects were muscle biopsied for gene and protein expression analysis. The fatigue index (FI) was 0.21 ± 0.27 and 0.91 ± 0.01 for the SCI and non-SCI groups, respectively, supporting that the low force protocol physiologically fatigued the chronically paralyzed muscle. The post fatigue potentiation index (PI) for the SCI group was increased to 1.60 ± 0.06 (P <0.001), while the non-SCI group was 1.26 ± 0.02 supporting that calcium handling was compromised with the low force stimulation. The mRNA expression from genes that regulate atrophy and fast properties (MSTN, ANKRD1, MYH8, and MYCBP2) was up regulated, while genes that regulate oxidative and slow muscle properties (MYL3, SDHB, PDK2, and RyR1) were repressed in the chronic SCI muscle. MSTN, ANKRD1, MYH8, MYCBP2 gene expression was also repressed 3 h after the low force stimulation protocol. Taken together, these findings support that a low force single twitch activation protocol induces paralyzed muscle fatigue and subsequent gene regulation. These findings suggest that training with a low force protocol may elicit skeletal muscle adaptations in people with SCI.
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Petrie
authors.affiliation: Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.
authors.forename: Manish
authors.initials: M
authors.lastname: Suneja
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Faidley
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa ; Department of Veterans Affairs, VA Medical Center, Iowa City, Iowa.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Shields
keywords: Electrical stimulation; genotype; paralysis; phenotype; potentiation
references.citation: Osteoporos Int. 2012 Sep;23(9):2335-46
references.pmid: 22187008
references.citation: Can J Physiol Pharmacol. 1996 Dec;74(12):1315-21
references.pmid: 9047041
references.citation: Disabil Rehabil. 2006 Jan 30;28(2):103-10
references.pmid: 16393840
references.citation: Compr Physiol. 2013 Jul;3(3):1337-62
references.pmid: 23897689
references.citation: J Cell Sci. 2012 May 1;125(Pt 9):2105-14
references.pmid: 22627029
references.citation: Biochem Biophys Res Commun. 1990 Jan 15;166(1):101-8
references.pmid: 2302193
references.citation: J Rehabil Res Dev. 2008;45(2):283-96
references.pmid: 18566946
references.citation: Cell Signal. 2009 Jan;21(1):128-35
references.pmid: 18955131
references.citation: FASEB J. 2004 Jun;18(9):1025-7
references.pmid: 15084522
references.citation: Biochem Biophys Res Commun. 1994 May 16;200(3):1277-82
references.pmid: 8185576
references.citation: PLoS One. 2013;8(2):e55542
references.pmid: 23418444
references.citation: Muscle Nerve. 2011 Jan;43(1):65-75
references.pmid: 21171097
references.citation: PLoS Biol. 2004 Oct;2(10):e348
references.pmid: 15486583
references.citation: Muscle Nerve. 2002 Nov;26(5):673-80
references.pmid: 12402290
references.citation: Diabetes Care. 2008 Apr;31(4):661-6
references.pmid: 18252901
references.citation: Arch Phys Med Rehabil. 2011 Jan;92(1):59-67
references.pmid: 21187206
references.citation: Am J Physiol. 1984 Nov;247(5 Pt 1):C462-71
references.pmid: 6548609
references.citation: PLoS One. 2009 Aug 11;4(8):e6575
references.pmid: 19668377
references.citation: Biochem Soc Trans. 2005 Apr;33(Pt 2):354-7
references.pmid: 15787605
references.citation: J Spinal Cord Med. 2013 May;36(3):191-9
references.pmid: 23809588
references.citation: J Appl Physiol (1985). 1987 May;62(5):2075-82
references.pmid: 3597276
references.citation: J Appl Physiol (1985). 2008 Jun;104(6):1574-82
references.pmid: 18436697
references.citation: J Neurophysiol. 1965 May;28:560-80
references.pmid: 14328454
references.citation: J Neurophysiol. 1995 Jun;73(6):2195-206
references.pmid: 7666132
references.citation: J Neurophysiol. 2006 Apr;95(4):2380-90
references.pmid: 16407424
references.citation: Arch Phys Med Rehabil. 2013 Dec;94(12):2559-2561
references.pmid: 23816924
references.citation: Pflugers Arch. 1996 Apr;431(6):882-7
references.pmid: 8927505
references.citation: Eur J Appl Physiol Occup Physiol. 1987;56(3):287-91
references.pmid: 3569237
references.citation: Physiol Genomics. 2013 Apr 16;45(8):321-31
references.pmid: 23444318
references.citation: Arch Phys Med Rehabil. 2008 Aug;89(8):1482-91
references.pmid: 18674984
references.citation: Adv Neurol. 1983;39:169-211
references.pmid: 6229158
references.citation: Clin Physiol. 2000 Nov;20(6):474-82
references.pmid: 11100395
references.citation: J Gen Physiol. 1979 Jul;74(1):1-16
references.pmid: 479818
references.citation: Arch Phys Med Rehabil. 2012 Jan;93(1):90-5
references.pmid: 22200386
references.citation: Arch Phys Med Rehabil. 1998 Sep;79(9):1133-6
references.pmid: 9749697
references.citation: Braz J Med Biol Res. 2000 May;33(5):499-508
references.pmid: 10775880
references.citation: Nat Genet. 2003 Jul;34(3):267-73
references.pmid: 12808457
references.citation: Pflugers Arch. 1997 Nov;434(6):848-51
references.pmid: 9306021
references.citation: Bone. 2004 May;34(5):869-80
references.pmid: 15121019
references.citation: Sports Med. 2013 Mar;43(3):179-94
references.pmid: 23338987
references.citation: J Electromyogr Kinesiol. 2008 Apr;18(2):308-16
references.pmid: 17157533
references.citation: J Electromyogr Kinesiol. 1997 Mar;7(1):3-13
references.pmid: 20719687
references.citation: Am J Physiol. 1988 Jul;255(1 Pt 1):C43-50
references.pmid: 3389401
references.citation: Pathobiology. 2002-2003;70(4):197-203
references.pmid: 12679596
references.citation: Muscle Nerve. 1998 Jun;21(6):776-87
references.pmid: 9585332
references.citation: Muscle Nerve. 2004 Dec;30(6):714-26
references.pmid: 15389717
references.citation: J Sci Med Sport. 2014 Jan;17(1):78-84
references.pmid: 23619159
references.citation: Am J Med Genet A. 2006 Dec 15;140(24):2797-801
references.pmid: 17103435
references.citation: Diabetes Metab J. 2012 Oct;36(5):328-35
references.pmid: 23130316
references.citation: J Appl Physiol (1985). 1993 Jul;75(1):382-8
references.pmid: 8397180
references.citation: J Rehabil Res Dev. 2013;50(2):193-202
references.pmid: 23761000
references.citation: Neurorehabil Neural Repair. 2007 Mar-Apr;21(2):169-79
references.pmid: 17312092
references.citation: J Appl Physiol (1985). 2013 Sep;115(6):785-93
references.pmid: 23788574
references.citation: PM R. 2012 Nov;4(11):797-804
references.pmid: 23174541
references.citation: J Appl Physiol (1985). 2006 Aug;101(2):556-65
references.pmid: 16575026
references.citation: Genomics. 1996 Nov 15;38(1):104-6
references.pmid: 8954790
references.citation: Scand J Rehabil Med. 1976;8(1):37-42
references.pmid: 132700
references.citation: Biochim Biophys Acta. 2014 Apr;1840(4):1285-94
references.pmid: 24345456
references.citation: Arch Phys Med Rehabil. 2012 May;93(5):790-5
references.pmid: 22444027
references.citation: J Spinal Cord Med. 2006;29(4):387-95
references.pmid: 17044389
references.citation: J Appl Physiol (1985). 1992 Apr;72(4):1393-400
references.pmid: 1317372
references.citation: J Appl Physiol (1985). 1997 May;82(5):1499-507
references.pmid: 9134899
references.citation: J Physiol. 1973 Nov;234(3):723-48
references.pmid: 4148752
references.citation: Neuromuscul Disord. 2012 Dec;22 Suppl 3:S162-7
references.pmid: 23182632