Premium
Anoxia induces Ca 2+ influx and loss of cell membrane integrity in rat extensor digitorum longus muscle
Author(s) -
Fredsted Anne,
Mikkelsen Ulla Ramer,
Gissel Hanne,
Clausen Torben
Publication year - 2005
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2005.030247
Subject(s) - extracellular , chemistry , stimulation , lactate dehydrogenase , calcium , medicine , endocrinology , skeletal muscle , incubation , extensor digitorum longus muscle , membrane potential , biophysics , biochemistry , biology , enzyme , organic chemistry
Anoxia can lead to skeletal muscle damage. In this study we have investigated whether an increased influx of Ca 2+ , 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% O 2 , 5% CO 2 ), anoxia (95% N 2 , 5% CO 2 ) or varying degrees of reduced oxygenation. At varying extracellular Ca 2+ concentrations ([Ca 2+ ] o ), 45 Ca influx and total cellular Ca 2+ 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 m m Ca 2+ , 15–75 min of exposure to anoxia increased 45 Ca influx by 46–129% ( P < 0.001) and Ca 2+ content by 20–50% ( P < 0.001). Mg 2+ (11.2 m m ) reduced the anoxia‐induced increase in 45 Ca influx by 43% ( P < 0.001). In muscles incubated at 20 and 5% O 2 , 45 Ca influx was also stimulated ( P < 0.001). Increasing [Ca 2+ ] o to 5 m m induced a progressive increase in both 45 Ca uptake and LDH release in resting anoxic muscles. When electrical stimulation was applied during anoxia, Ca 2+ content and LDH release increased markedly and showed a significant correlation( r 2 = 0.55, P < 0.001). In conclusion, anoxia or incubation at 20 or 5% O 2 leads to an increased influx of 45 Ca. This is associated with a loss of cell membrane integrity, possibly initiated by Ca 2+ . The loss of cell membrane integrity further increases Ca 2+ influx, which may elicit a self‐amplifying process of cell membrane leakage.