Reactive oxygen species reduce myofibrillar Ca2+ sensitivity in fatiguing mouse skeletal muscle at 37 degrees C.
The mechanisms of muscle fatigue were studied in small muscle bundles and single fibres isolated from the flexor digitorum brevis of the mouse. Fatigue caused by repeated isometric tetani was accelerated at body temperature (37 degrees C) when compared to room temperature (22 degrees C). The membrane-permeant reactive oxygen species (ROS) scavenger, Tiron (5 mM), had no effect on the rate of fatigue at 22 degrees C but slowed the rate of fatigue at 37 degrees C to that observed at 22 degrees C. Single fibres were microinjected with indo-1 to measure intracellular calcium. In the accelerated fatigue at 37 degrees C the tetanic [Ca2+](i) did not change significantly and the decline of maximum Ca2+-activated force was similar to that observed at 22 degrees C. The cause of the greater rate of fatigue at 37 degrees C was a large fall in myofibrillar Ca2+ sensitivity. In the presence of Tiron, the large fall in Ca2+ sensitivity was abolished and the usual decline in tetanic [Ca2+](i) was observed. This study confirms the importance of ROS in fatigue at 37 degrees C and shows that the mechanism of action of ROS is a decline in myofibrillar Ca2+ sensitivity.
Moopanar
Terence R
TR
Institute for Biomedical Sciences, School of Medical Sciences, University of Sydney F13, NSW 2006, Australia.
Allen
David G
DG
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000737:chemistry; D066298:In Vitro Techniques; D051379:Mice; D018763:Muscle Fatigue / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D002110:Caffeine; D002118:Calcium
Cell Calcium. 1999 Mar;25(3):227-35
10378084
J Physiol. 1998 Jun 1;509 ( Pt 2):565-75
9575304
Pflugers Arch. 2000 May;440(1):163-70
10864011
J Appl Physiol (1985). 2001 Jan;90(1):45-54
11133892
FASEB J. 2001 Feb;15(2):309-11
11156946
J Appl Physiol (1985). 2001 Feb;90(2):724-31
11160074
Exp Physiol. 2001 Mar;86(2):161-8
11429630
J Physiol. 2002 Nov 1;544(Pt 3):765-76
12411522
J Physiol. 2003 Jan 1;546(Pt 1):149-63
12509485
J Physiol. 2003 Mar 15;547(Pt 3):807-23
12562929
Free Radic Biol Med. 2003 Sep 1;35(5):455-64
12927595
Am J Physiol Cell Physiol. 2004 Sep;287(3):C673-81
15128502
Circ Res. 1998 Aug 24;83(4):423-30
9721699
J Physiol. 2001 Nov 1;536(Pt 3):657-65
11691862
Am J Physiol Regul Integr Comp Physiol. 2004 Oct;287(4):R698-705
15178539
J Physiol. 2004 Oct 15;560(Pt 2):451-68
15308682
J Physiol. 1973 Nov;234(3):723-48
4148752
J Physiol. 1978 Mar;276:233-55
25957
J Biol Chem. 1985 Mar 25;260(6):3440-50
3838314
J Physiol. 1987 Sep;390:285-93
3443937
J Physiol. 1989 May;412:155-80
2600830
Cell Calcium. 1991 Jan;12(1):11-8
1901763
J Gen Physiol. 1991 Sep;98(3):615-35
1761971
Arch Biochem Biophys. 1992 Apr;294(1):98-106
1312813
J Appl Physiol (1985). 1992 Nov;73(5):1797-804
1474054
J Physiol. 1993 Jan;460:1-13
8487190
J Physiol. 1993 Jul;466:611-28
8410709
Physiol Rev. 1994 Jan;74(1):49-94
8295935
J Appl Physiol (1985). 1994 Jul;77(1):317-24
7961253
J Clin Invest. 1994 Dec;94(6):2468-74
7989604
J Physiol. 1995 Jan 1;482 ( Pt 1):123-40
7730977
J Physiol. 1995 Aug 1;486 ( Pt 3):689-94
7473229
J Biol Chem. 1995 Oct 27;270(43):25557-63
7592726
Exp Physiol. 1995 Jul;80(4):497-527
7576593
J Physiol. 1995 Sep 1;487 ( Pt 2):331-42
8558467
Circ Res. 1996 Mar;78(3):455-65
8593704
J Biol Chem. 1996 Oct 18;271(42):26026-31
8824242
J Appl Physiol (1985). 1996 Aug;81(2):731-7
8872640
J Physiol. 1997 Jan 1;498 ( Pt 1):17-29
9023765
J Physiol. 1997 Apr 1;500 ( Pt 1):193-204
9097943
Am J Respir Crit Care Med. 1997 Jul;156(1):140-5
9230738
Mol Cell Biochem. 1998 Feb;179(1-2):99-110
9543353
Acta Physiol Scand. 1999 Jun;166(2):111-21
10383490