Role of calcium in triggering rapid ultrastructural damage in muscle: a study with chemically skinned fibres.
Agents (A23187, caffeine) believed to raise [Ca]i in vertebrate cardiac and skeletal muscles cause rapid and characteristic subcellular damage in vitro and in vivo. By using saponin-skinned amphibian pectoris cutaneous muscle and Ca-EGTA-buffered solutions it is shown that low [Ca] consistently triggers the same rapid (2-20 min), ultrastructural damage. Electron micrographs reveal a close similarity between the damaged intact and skinned preparations, namely loss of myofilament organization, specific Z-line damage, dissolution and hypercontraction bands, characteristic mitochondrial swelling and division. Where both actin and myosin filaments were lost, an underlying cytoskeletal network frequently remained, still attached to the Z-line framework. Ca was effective in skinned preparations from 5 X 10(-7) M to 8 X 10(-6) M, within the concentration range experienced by a contracting muscle. Damage was [Ca]- and time-dependent and it is suggested that it is probably the active movement of Ca ions across key membrane sites that is critical in triggering damage of the myofilament apparatus. Strontium can substitute for Ca at higher concentrations. The action of saponin suggests that the chemically skinned cell is partially activated. Ca-triggering can be bypassed experimentally by membrane-active agents or by sulphydryl agents. Ruthenium Red and trifluoperazine indirectly cause damage in the intact cell by raising [Ca]i. Studies with saponin-skinned cells and protease inhibitors show that changes in pHi, loss of ATP, Ca-activated neutral protease, or release of lysosomal enzymes (cathepsins B, D, L or H), are not involved in characteristic rapid myofilament damage.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D008854:Microscopy, Electron; D009132:Muscles / Q000187:drug effects* / Q000648:ultrastructure; D011894:Rana pipiens; D011896:Rana temporaria; D012503:Saponins / Q000494:pharmacology; D013997:Time Factors
D012503:Saponins; D000001:Calcimycin; D002118:Calcium