title: Low-frequency stimulation regulates metabolic gene expression in paralyzed muscle.
abstract: The altered metabolic state after a spinal cord injury compromises systemic glucose regulation. Skeletal muscle atrophies and transforms into fast, glycolytic, and insulin-resistant tissue. Osteoporosis is common after spinal cord injury and limits the ability to exercise paralyzed muscle. We used a novel approach to study the acute effect of two frequencies of stimulation (20 and 5 Hz) on muscle fatigue and gene regulation in people with chronic paralysis. Twelve subjects with chronic (>1 yr) and motor complete spinal cord injury (ASIA A) participated in the study. We assessed the twitch force before and after a single session of electrical stimulation (5 or 20 Hz). We controlled the total number of pulses delivered for each protocol (10,000 pulses). Three hours after the completion of the electrical stimulation (5 or 20 Hz), we sampled the vastus lateralis muscle and examined genes involved with metabolic transcription, glycolysis, oxidative phosphorylation, and mitochondria remodeling. We discovered that the 5-Hz stimulation session induced a similar amount of fatigue and a five- to sixfold increase (P < 0.05) in key metabolic transcription factors, including PGC-1α, NR4A3, and ABRA as the 20-Hz session. Neither session showed a robust regulation of genes for glycolysis, oxidative phosphorylation, or mitochondria remodeling. We conclude that a low-force and low-frequency stimulation session is effective at inducing fatigue and regulating key metabolic transcription factors in human paralyzed muscle. This strategy may be an acceptable intervention to improve systemic metabolism in people with chronic paralysis.
authors: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, Iowa City, Iowa;
authors: Michael
authors: M
authors: Petrie
authors: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa; and.
authors: Manish
authors: M
authors: Suneja
authors: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, Iowa City, Iowa; Department of Veterans Affairs, Veterans Affairs Medical Center, Iowa City, Iowa richard-shields@uiowa.edu.
authors: Richard K
authors: RK
authors: Shields
mesh_terms: D004558:Electric Stimulation / Q000379:methods; D004599:Electric Stimulation Therapy / Q000379:methods; D015870:Gene Expression / Q000502:physiology*; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D018763:Muscle Fatigue / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology*; D010085:Oxidative Phosphorylation; D010243:Paralysis / Q000378:metabolism* / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology*
keywords: diabetes; electrical stimulation; health quality; metabolic syndrome; spinal cord injury
references: J Appl Physiol (1985). 2009 Jun;106(6):1826-31
references: 19359610
references: J Rehabil Res Dev. 2008;45(2):283-96
references: 18566946
references: J Musculoskelet Neuronal Interact. 2008 Jul-Sep;8(3):227-38
references: 18799855
references: J Appl Physiol (1985). 1997 May;82(5):1499-507
references: 9134899
references: J Spinal Cord Med. 2012 May;35(3):140-7
references: 22507023
references: Diabetes Care. 2011 Feb;34(2):497-503
references: 21270206
references: Sports Med. 2007;37(9):737-63
references: 17722947
references: J Electromyogr Kinesiol. 1997 Mar;7(1):3-13
references: 20719687
references: Am J Hum Genet. 2013 Aug 8;93(2):384-9
references: 23910460
references: PLoS One. 2013;8(2):e55542
references: 23418444
references: Clin Neuropathol. 1986 Mar-Apr;5(2):73-7
references: 3708956
references: J Bone Miner Res. 2014 Feb;29(2):432-9
references: 23873733
references: J Neurophysiol. 1995 Jun;73(6):2195-206
references: 7666132
references: J Exp Biol. 1985 Mar;115:105-12
references: 3161974
references: Diabetes. 1980 Nov;29(11):906-10
references: 7429029
references: J Neurophysiol. 1984 Sep;52(3):410-20
references: 6481439
references: Biochem Soc Trans. 2005 Apr;33(Pt 2):354-7
references: 15787605
references: J Spinal Cord Med. 2014 May;37(3):349-54
references: 24621022
references: Biochem Biophys Res Commun. 2008 Aug 8;372(4):584-8
references: 18501704
references: Arch Phys Med Rehabil. 1983 Mar;64(3):107-10
references: 6338859
references: Biochem Biophys Res Commun. 1994 May 16;200(3):1277-82
references: 8185576
references: Muscle Nerve. 2011 Jan;43(1):65-75
references: 21171097
references: Ann N Y Acad Sci. 2012 Oct;1271:110-7
references: 23050972
references: J Cardiopulm Rehabil Prev. 2011 Mar-Apr;31(2):73-80
references: 21045711
references: Hum Genet. 2004 Jul;115(2):123-7
references: 15138885
references: J Clin Endocrinol Metab. 2013 May;98(5):2027-36
references: 23515448
references: Nat Genet. 2003 Jul;34(3):267-73
references: 12808457
references: J Physiol. 2006 Aug 1;574(Pt 3):889-903
references: 16690701
references: Diabetes. 2000 Jul;49(7):1092-5
references: 10909963
references: Diabetes Care. 2012 May;35(5):976-83
references: 22374636
references: Adv Neurol. 1983;39:169-211
references: 6229158
references: J Clin Invest. 2006 Mar;116(3):615-22
references: 16511594
references: Hum Mol Genet. 2012 Jul 15;21(14):3193-204
references: 22505582
references: J Sci Med Sport. 2014 Jan;17(1):78-84
references: 23619159
references: J Appl Physiol (1985). 2007 Feb;102(2):529-40
references: 17082363
references: Metabolism. 2014 Apr;63(4):441-51
references: 24559845
references: Arch Phys Med Rehabil. 1998 Sep;79(9):1133-6
references: 9749697
references: Am J Physiol. 1999 Dec;277(6 Pt 2):R1690-6
references: 10600915
references: Am J Physiol Endocrinol Metab. 2012 Mar 15;302(6):E731-9
references: 22252943
references: Osteoporos Int. 2012 Sep;23(9):2335-46
references: 22187008
references: Proc Nutr Soc. 2004 May;63(2):279-86
references: 15294044
references: J Spinal Cord Med. 2013 May;36(3):191-9
references: 23809588
references: Diabetes Care. 2008 Apr;31(4):661-6
references: 18252901
references: Neurosci Lett. 1983 Mar 28;36(1):55-8
references: 6856203
references: J Muscle Res Cell Motil. 2003;24(2-3):121-6
references: 14609023
references: Arch Phys Med Rehabil. 2005 Jul;86(7):1502-4
references: 16003691
references: Science. 2012 Jul 6;337(6090):96-100
references: 22628558
references: PLoS One. 2009;4(8):e6575
references: 19668377
references: PLoS One. 2013;8(8):e71623
references: 23951207
references: Physiol Rep. 2014 Feb 25;2(2):e00248
references: 24744911
references: J Orthop Sports Phys Ther. 2002 Feb;32(2):65-74
references: 11838582
references: Am J Physiol. 1990 Oct;259(4 Pt 1):E593-8
references: 1699426
references: Exp Gerontol. 2014 Aug;56:182-8
references: 24486129
references: J Neurophysiol. 2006 Apr;95(4):2380-90
references: 16407424
references: Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10496-500
references: 7479827
references: J Physiol. 2010 May 15;588(Pt 10):1779-90
references: 20308248
references: Muscle Nerve. 2013 Dec;48(6):963-70
references: 23494933
references: Am J Physiol Regul Integr Comp Physiol. 2011 Jun;300(6):R1303-10
references: 21451146