Am J Physiol Cell Physiol AJP: Renal Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 QUICK SEARCH:   [advanced]


     


Am J Physiol Cell Physiol (November 23, 2005). doi:10.1152/ajpcell.00469.2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
290/4/C1199    most recent
00469.2005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Verburg, E.
Right arrow Articles by Lamb, G. D
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Verburg, E.
Right arrow Articles by Lamb, G. D
Submitted on September 20, 2005
Accepted on November 17, 2005

Long-lasting muscle fatigue: partial disruption of excitation-contraction coupling by the elevated cytosolic [Ca2+] during contractions

Esther Verburg1*, Travis L Dutka1, and Graham D Lamb1

1 Zoology, Latrobe University, Melbourne, Vic, Australia

* To whom correspondence should be addressed. E-mail: e.verburg{at}latrobe.edu.au.

The repeated elevation of cytosolic [Ca2+] above resting levels during contractile activity has been associated with long-lasting muscle fatigue. The mechanism underlying this fatigue appears to involve elevated levels of cytosolic [Ca2+] inducing disruption of the excitation-contraction (EC) coupling process at the triad junction. It is however unclear what aspects of the activity-related [Ca2+] changes are responsible for the deleterious effects, in particular whether it depends primarily on the peak [Ca2+] reached locally at particular sites or on the temporal summation of the increased [Ca2+] in the cytoplasm as a whole. In this study we used mechanically-skinned fibers from rat extensor digitorum longus muscle, in which the normal EC-coupling process remains intact. The cytosolic [Ca2+] was raised, either by applying a set elevated [Ca2+] throughout the fiber or by using action-potential stimulation to induce release of sarcoplasmic reticulum Ca2+ by the normal EC-coupling system with or without augmentation by caffeine or buffering with BAPTA. We show that elevating the [Ca2+] in the physiological range of 2-20µM irreversibly disrupts EC-coupling in a concentration-dependent manner, but requires exposure for a relatively long time (1-3 min) to cause substantial uncoupling. The effectiveness of Ca2+ released via the endogenous system in disrupting EC-coupling indicates that the relatively high [Ca2+] attained close to the release site in the triad junction is a more important factor than the increase in the bulk cytoplasmic [Ca2+]. Our results suggest that during prolonged vigorous activity, the many repeated episodes of relatively high triadic [Ca2+] can disrupt EC-coupling and lead to long-lasting fatigue.




This article has been cited by other articles:


Home page
Am. J. Physiol. Cell Physiol.Home page
E. Verburg, R. M. Murphy, I. Richard, and G. D. Lamb
Involvement of calpains in Ca2+-induced disruption of excitation-contraction coupling in mammalian skeletal muscle fibers
Am J Physiol Cell Physiol, May 1, 2009; 296(5): C1115 - C1122.
[Abstract] [Full Text] [PDF]


Home page
J. Physiol.Home page
R. M. Murphy, T. L. Dutka, and G. D. Lamb
Hydroxyl radical and glutathione interactions alter calcium sensitivity and maximum force of the contractile apparatus in rat skeletal muscle fibres
J. Physiol., April 15, 2008; 586(8): 2203 - 2216.
[Abstract] [Full Text] [PDF]


Home page
J. Physiol.Home page
T. L. Dutka, R. M. Murphy, D. G. Stephenson, and G. D. Lamb
Chloride conductance in the transverse tubular system of rat skeletal muscle fibres: importance in excitation-contraction coupling and fatigue
J. Physiol., February 1, 2008; 586(3): 875 - 887.
[Abstract] [Full Text] [PDF]


Home page
Physiol. Rev.Home page
D. G. Allen, G. D. Lamb, and H. Westerblad
Skeletal Muscle Fatigue: Cellular Mechanisms
Physiol Rev, January 1, 2008; 88(1): 287 - 332.
[Abstract] [Full Text] [PDF]


Home page
J. Appl. Physiol.Home page
D. G. Allen, G. D. Lamb, and H. Westerblad
Impaired calcium release during fatigue
J Appl Physiol, January 1, 2008; 104(1): 296 - 305.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Cell Physiol.Home page
T. L. Dutka and G. D. Lamb
Na+-K+ pumps in the transverse tubular system of skeletal muscle fibers preferentially use ATP from glycolysis
Am J Physiol Cell Physiol, September 1, 2007; 293(3): C967 - C977.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Cell Physiol.Home page
T. L. Dutka and G. D. Lamb
Transverse tubular system depolarization reduces tetanic force in rat skeletal muscle fibers by impairing action potential repriming
Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2112 - C2121.
[Abstract] [Full Text] [PDF]


Home page
J. Physiol.Home page
R. M. Murphy, E. Verburg, and G. D. Lamb
Ca2+ activation of diffusible and bound pools of {micro}-calpain in rat skeletal muscle
J. Physiol., October 15, 2006; 576(2): 595 - 612.
[Abstract] [Full Text] [PDF]


Home page
J. Appl. Physiol.Home page
G. D. Lamb and D. G. Stephenson
The Last Word: Point:Counterpoint authors respond to commentaries on "Lactic acid accumulation is an advantage/disadvantage during muscle activity"
J Appl Physiol, July 1, 2006; 101(1): 369 - 369.
[Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.