Decrease in cytoskeleton-bound phosphofructokinase in muscle induced by high intracellular calcium, serotonin and phospholipase A2 in vivo.

1. Particulate (cytoskeleton-bound) and soluble phosphofructokinase (PFK), separated from rat muscle, exhibited different allosteric properties; in contrast to the soluble PFK, the bound enzyme was not sensitive to allosteric regulation. 2. Treatment of muscle with Ca2(+)-ionophore A23187, serotonin, or phospholipase A2, reduced the binding of PFK and aldolase. 3. The decrease in enzymes' binding was most probably mediated by the rise in free intracellular Ca2+ induced by these agents, as we found that direct addition of Ca2+ to the particulate fraction of muscle, caused solubilization of bound PFK and aldolase. 4. The reduction in binding of PFK and aldolase to cytoskeletal proteins, may have a deleterious effect on muscle function and structure, and may be involved in the mechanism of muscle damage in pathological conditions where accumulation of Ca2+ occurs.