Pflügers Archiv

, Volume 442, Issue 5, pp 738–744

Hypoxia/fatigue-induced degradation of troponin I and troponin C: new insights into physiologic muscle fatigue

  • Marco de Paula Brotto
  • Sheila Van Leyen
  • Leticia S. Brotto
  • Jian-Ping Jin
  • Christopher M. Nosek
  • Thomas M. Nosek
Original Article

DOI: 10.1007/s004240100587

Cite this article as:
de Paula Brotto, M., Van Leyen, S., Brotto, L.S. et al. Pflügers Arch - Eur J Physiol (2001) 442: 738. doi:10.1007/s004240100587

Abstract.

Conditions such as respiratory failure and cardiopulmonary arrest can expose the diaphragm to hypoxemia. In skeletal muscles, fatiguing stimulation renders muscles hypoxic, which has long been known to dramatically reduce muscle function. We have previously demonstrated that fatiguing stimulation under hypoxic conditions disrupts both the excitation-contraction coupling (ECC) process and the isometric contractile properties (ICP) in intact diaphragm muscle strips and the contractile properties of skinned fibers isolated from these muscles. Here we have analyzed the effects of intermittent fatiguing stimulation on specific muscle proteins in muscle strips from mouse diaphragms that have been exposed to hypoxia. We report for the first time that the effects of hypoxia-fatigue, namely to decrease maximal tetanic force, maximal calcium-activated force and calcium sensitivity of the mouse diaphragm muscle, are associated with the degradation of troponins TnI and TnC (Western blot analysis). The concentrations of TnT and actin did not change under these same conditions. Because troponins are integrally involved in regulating the interaction between actin and myosin during the cross-bridge cycle, the degradation of TnI and TnC may explain the effects of hypoxia-fatigue on the ICP. This interpretation is supported by the observations that extraction of troponins from control skinned fibers mimics the effects of hypoxia-fatigue on contractile function and that incorporation of native troponins into fibers isolated from hypoxic-fatigued muscles partially restores function.

Fatigue Skeletal muscle Skinned fibers Troponin I Troponin C 

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Marco de Paula Brotto
    • 1
  • Sheila Van Leyen
    • 1
  • Leticia S. Brotto
    • 1
  • Jian-Ping Jin
    • 1
  • Christopher M. Nosek
    • 1
  • Thomas M. Nosek
    • 1
  1. 1.Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA