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This Article Full Text Full Text (PDF) All Versions of this Article: 90/5/703    most recent expphysiol.2005.030247v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fredsted, A. Articles by Clausen, T. Search for Related Content PubMed PubMed Citation Articles by Fredsted, A. Articles by Clausen, T. Related Collections Muscle

¹ Department of Physiology, University of Aarhus, Århus, Denmark

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.

(Received 21 February 2005; accepted after revision 13 May 2005; first published online 20 May 2005)
Corresponding author A. Fredsted: Department of Physiology, University of Aarhus, Ole Worms Allé 160, DK-8000 Århus C, Denmark. Email: af{at}fi.au.dk

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