Experimental skeletal muscle damage: the nature of the calcium-activated degenerative processes.
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.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008931:Mitochondria, Muscle / Q000378:metabolism; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009135:Muscular Diseases / Q000209:etiology*; D010447:Peptide Hydrolases / Q000502:physiology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology
D011480:Protease Inhibitors; D010741:Phospholipases A; D010447:Peptide Hydrolases; D002118:Calcium