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Anoxia induces Ca2+ influx and loss of cell membrane integrity in rat extensor digitorum longus muscle.
- Source :
-
Experimental physiology [Exp Physiol] 2005 Sep; Vol. 90 (5), pp. 703-14. Date of Electronic Publication: 2005 May 20. - Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- Animals
Cell Membrane drug effects
Cell Membrane pathology
Electric Stimulation
Female
Hindlimb
Hypoxia pathology
In Vitro Techniques
L-Lactate Dehydrogenase metabolism
Male
Oxygen pharmacology
Rats
Rats, Wistar
Toes
Calcium metabolism
Hypoxia physiopathology
Muscle, Skeletal pathology
Muscle, Skeletal physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 0958-0670
- Volume :
- 90
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Experimental physiology
- Publication Type :
- Academic Journal
- Accession number :
- 15908508
- Full Text :
- https://doi.org/10.1113/expphysiol.2005.030247