Document Detail

Anoxia induces Ca2+ influx and loss of cell membrane integrity in rat extensor digitorum longus muscle.
MedLine Citation:
PMID:  15908508     Owner:  NLM     Status:  MEDLINE    
Anoxia can lead to skeletal muscle damage. In this study we have investigated whether an increased influx of Ca2+, which is known to cause damage during electrical stimulation, is a causative factor in anoxia-induced muscle damage. Isolated extensor digitorum longus (EDL) muscles from 4-week-old Wistar rats were mounted at resting length and were either resting or stimulated (30 min, 40 Hz, 10 s on, 30 s off) in the presence of standard oxygenation (95% O2, 5% CO2), anoxia (95% N2, 5% CO2) or varying degrees of reduced oxygenation. At varying extracellular Ca2+ concentrations ([Ca2+]o), 45Ca influx and total cellular Ca2+ content were measured and the release of lactic acid dehydrogenase (LDH) was determined as an indicator of cell membrane leakage. In resting muscles, incubated at 1.3 mM Ca2+, 15-75 min of exposure to anoxia increased 45Ca influx by 46-129% (P<0.001) and Ca2+ content by 20-50% (P<0.001). Mg2+ (11.2 mM) reduced the anoxia-induced increase in 45Ca influx by 43% (P<0.001). In muscles incubated at 20 and 5% O2, 45Ca influx was also stimulated (P<0.001). Increasing [Ca2+]o to 5 mM induced a progressive increase in both 45Ca uptake and LDH release in resting anoxic muscles. When electrical stimulation was applied during anoxia, Ca2+ content and LDH release increased markedly and showed a significant correlation (r2=0.55, P<0.001). In conclusion, anoxia or incubation at 20 or 5% O2 leads to an increased influx of 45Ca. This is associated with a loss of cell membrane integrity, possibly initiated by Ca2+. The loss of cell membrane integrity further increases Ca2+ influx, which may elicit a self-amplifying process of cell membrane leakage.
Anne Fredsted; Ulla Ramer Mikkelsen; Hanne Gissel; Torben Clausen
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-05-20
Journal Detail:
Title:  Experimental physiology     Volume:  90     ISSN:  0958-0670     ISO Abbreviation:  Exp. Physiol.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-22     Completed Date:  2005-11-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9002940     Medline TA:  Exp Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  703-14     Citation Subset:  IM    
Department of Physiology, University of Aarhus, Ole Worms Allé 160, DK-8000 Arhus C, Denmark.
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MeSH Terms
Anoxia / pathology,  physiopathology*
Calcium / metabolism*
Cell Membrane / drug effects,  pathology
Electric Stimulation
L-Lactate Dehydrogenase / secretion
Muscle, Skeletal / pathology*,  physiopathology*
Oxygen / pharmacology
Rats, Wistar
Reg. No./Substance:
7440-70-2/Calcium; 7782-44-7/Oxygen; EC Dehydrogenase

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