Details

Autor(en) / Beteiligte

• Verburg, Esther
• Dutka, Travis L
• Lamb, Graham D

Titel

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

Ist Teil von

• American Journal of Physiology: Cell Physiology, 2006-04, Vol.290 (4), p.C1199-C1208

Ort / Verlag

United States

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• Department of Zoology, La Trobe University, Bundoora Campus, Melbourne, Victoria, Australia Submitted 20 September 2005 ; accepted in final form 17 November 2005 The repeated elevation of cytosolic Ca 2+ concentration ([Ca 2+ ] i ) above resting levels during contractile activity has been associated with long-lasting muscle fatigue. The mechanism underlying this fatigue appears to involve elevated [Ca 2+ ] i levels that induce disruption of the excitation-contraction (E-C) coupling process at the triad junction. Unclear, however, are which aspects of the activity-related [Ca 2+ ] i changes are responsible for the deleterious effects, in particular whether they depend primarily on the peak [Ca 2+ ] i reached locally at particular sites or on the temporal summation of the increased [Ca 2+ ] in the cytoplasm as a whole. In this study, we used mechanically skinned fibers from rat extensor digitorum longus muscle, in which the normal E-C coupling process remains intact. The [Ca 2+ ] i was raised either by applying a set elevated [Ca 2+ ] throughout the fiber or by using action potential stimulation to induce the release of sarcoplasmic reticulum Ca 2+ by the normal E-C coupling system with or without augmentation by caffeine or buffering with BAPTA. Herein we show that elevating [Ca 2+ ] i in the physiological range of 2–20 µM irreversibly disrupts E-C coupling in a concentration-dependent manner but requires exposure for a relatively long time (1–3 min) to cause substantial uncoupling. The effectiveness of Ca 2+ released via the endogenous system in disrupting E-C coupling indicates that the relatively high [Ca 2+ ] i attained close to the release site at the triad junction is a more important factor than the increase in bulk [Ca 2+ ] i . Our results suggest that during prolonged vigorous activity, the many repeated episodes of relatively high triadic [Ca 2+ ] can disrupt E-C coupling and lead to long-lasting fatigue. skeletal muscle; low-frequency fatigue; ryanodine receptor; skinned fiber Address for reprint requests and other correspondence: E. Verburg, Dept. of Zoology, La Trobe Univ., Bundoora Campus, Melbourne, Victoria 3086, Australia (e-mail: e.verburg{at}latrobe.edu.au )