Role of the calcium-calpain pathway in cytoskeletal damage after eccentric contractions

Bao Ting Zhang, Simon S. Yeung, David G. Allen, Ling Qin, Wai Ella Yeung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

51 Citations (Scopus)

Abstract

The mechanism(s) underlying eccentric damage to skeletal muscle cytoskeleton remain unclear. We examined the role of Ca2+influx and subsequent calpain activation in eccentric damage to cytoskeletal proteins. Eccentric muscle damage was induced by stretching isolated mouse muscles by 20% of the optimal length in a series of 10 tetani. Muscle force and immunostaining of the cytoskeletal proteins desmin, dystrophin, and titin were measured at 5, 15, 30, and 60 min after eccentric contractions and compared with the control group that was subjected to 10 isometric contractions. A Ca2+-free solution and leupeptin (100 μM), a calpain inhibitor, were applied to explore the role of Ca2+and calpain, respectively, in eccentric muscle damage. After eccentric contractions, decreases in desmin and dystrophin immunostaining were apparent after 5 min that accelerated over the next 60 min. Increased titin immunostaining, thought to indicate damage to titin, was evident 10 min after stretch, and fibronectin entry, indicating membrane disruption, was evident 20 min after stretch. These markers of damage also increased in a time-dependent manner. Muscle force was reduced immediately after stretch and continued to fall, reaching 56 ± 2% after 60 min. Reducing extracellular calcium to zero or applying leupeptin minimized the changes in immunostaining of cytoskeletal proteins, reduced membrane disruption, and improved the tetanic force. These results suggest that the cytoskeletal damage and membrane disruption were mediated primarily by increased Ca2+influx into muscle cells and subsequent activation of calpain.
Original languageEnglish
Pages (from-to)352-357
Number of pages6
JournalJournal of Applied Physiology
Volume105
Issue number1
DOIs
Publication statusPublished - 1 Jul 2008

Keywords

  • Calcium-activated protease
  • Calpain
  • Cytoskeleton
  • Muscle damage

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this