Excitation-induced Ca2+ influx and skeletal muscle cell damage.
Excessive exercise may lead to skeletal muscle cell damage with degradation of cellular components and leakage of intracellular enzymes. Calcium has repeatedly been proposed to be involved in these processes. Studies have shown that the resting level of cytoplasmic Ca2+ increases up to threefold during long-term low-frequency stimulation. We have shown that electrical stimulation produces a marked increase in Ca2+ uptake and Ca2+ content in rat skeletal muscle, both in vivo and in vitro. Continuous stimulation for 240 min at 1 Hz results in an increased release (18-fold) of lactate dehydrogenase (LDH) from extensor digitorum longus (EDL) muscle. This was associated with an increased total Ca2+ content (185%), was augmented at high [Ca2+]o and suppressed at low [Ca2+]o. The release of LDH may reflect partial loss of sarcolemmal integrity as a result of degradation of membrane components by Ca2+-activated enzymes (e.g. calpain or phospholipase A2). After cessation of stimulation the increased release of LDH continues for at least 120 min. This is associated with an up to sevenfold increase in 45Ca uptake. The increased permeability to Ca2+ may further activate calpain and phospholipase A2 and accelerate the loss of membrane integrity. Stimulation-induced uptake of Ca2+ and release of LDH is most pronounced in EDL (mainly composed of fast-twitch fibres at variance with soleus which is mainly composed of slow-twitch fibres). This may account for the observation that prolonged exercise leads to preferential damage to fast-twitch fibres. We hypothesize that excessive exercise may lead to an intracellular accumulation of Ca2+ and increased cytoplasmic Ca2+ causing activation of self-accelerating degradative pathways leading to muscle damage.
Gissel
H
H
Department of Physiology, University of Aarhus, Arhus C, Denmark.
Clausen
T
T
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004558:Electric Stimulation; D006801:Humans; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D007770:L-Lactate Dehydrogenase; D010741:Phospholipases A; D054467:Phospholipases A2; D002154:Calpain; D002118:Calcium