Experimental skeletal muscle damage: the nature of the calcium‐activated degenerative processes

Abstract

The role of calcium-activated degenerative processes in the efflux of enzyme from experimentally damaged mouse muscle has been studied using an isolated mouse soleus muscle preparation. Inhibition of mitochondrial activity with dinitrophenol or sodium cyanide was found to cause a large efflux of enzyme. This was largely prevented by withdrawal of the extracellular calcium suggesting that mitochondrial calcium overload does not play a major role in the damage leading to enzyme efflux. Treatment of the muscles with a variety of protease inhibitors had no effect on the enzyme efflux from muscles following exhaustive contractile activity indicating that activation of protease activity is not a major factor in the damaging process. Certain inhibitors of phospholipase-A activity (i.e. dibucaine, chlorpromazine and mepacrine) have been found to significantly reduce the enzyme efflux following treatment of the muscles with dinitrophenol, although other phospholipase inhibitors were without effect. It is suggested that the changes in muscle membrane permeability leading to enzyme efflux following experimental muscle damage are probably the result of calcium-mediated activation of phospholipase A leading to changes in membrane phospholipid metabolism.

Ca2+ uptake and cellular integrity in rat EDL muscle exposed to electrostimulation, electroporation, or A23187

“…The present observations confirm and extend previous studies (17,20,21) in documenting that Ca 2ϩ gaining access to the cytoplasm from the extracellular phase elicits loss of cellular integrity. The new aspect is that this process seems to be self-increasing, which possibly leads to more extensive muscle damage.…”

“…Moreover, we have recently measured a significant 21% increase in the Ca 2ϩ content of vastus lateralis muscle of human subjects after a 100-km run (27). Ca 2ϩ ions have been shown to activate intracellular phospholipases (20) and proteases (3,4). These enzymes in turn degrade cellular lipids, proteins, and membranes and eventually lead to sarcolemmal leakage and loss of intracellular components to the surrounding water phase (21).…”

“…Because membrane damage allows further influx of Ca 2ϩ , this results in positive feedback that may further increase membrane degeneration. Ca 2ϩ -ionophore; skeletal; extensor digitorum longus; lactate dehydrogenase EVIDENCE IS ACCUMULATING THAT Ca 2ϩ plays a significant role in the loss of muscle cell integrity associated with intense exercise (2,3,16,20,21). During contractile activity, Ca 2ϩ ions are primarily mobilized into the cytoplasm by release from the sarcoplasmic reticulum (SR).…”

Properties of single FDB fibers following a collagenase digestion for studying contractility, fatigue, and pCa-sarcomere shortening relationship

“…Exposing rat FDB single fibers to 404 mosmol/l by adding sucrose leads to membrane depolarization and sarcoplasmic reticulum Ca 2Ϯ release (43). Thus, it is possible that fiber morphology and contractility are affected by DMEM because of a decreased membrane excitability related to the depolarization (50) and fiber damage associated with large [Ca 2ϩ ]i (27,32). The culture media used in this study were supplemented with a standard 10% (vol/vol) FBS concentration, which increased the number of viable fibers.…”

Ca2+ loading reduces the tensile strength of sarcolemmal vesicles shed from rabbit muscle.

“…Segmental necrosis in skeletal muscle, e.g. after unaccustomed eccentric exercise, or in myopathy, has similarly been ascribed to elevated cytosolic [Ca2+] (Jackson, Jones & Edwards, 1984 (Verhoven, Schlegel & Williamson, 1992;Williamson, Kulick, Zachowski, Schlegel & Devaux, 1992 (Evans & Needham, 1986). …”