Comparative studies on the role of calcium in triggering subcellular damage in cardiac muscle

Abstract

1. 1. Isolated cardiac muscle strips from amphibians and mammals, together with isolated frog hearts, have been used as model systems for studying the action of elevated [Ca 2+] i in promoting severe damage. 2. 2. A23187 and caffeine are believed to cause a rise in [Ca 2+] i 3. 3. Elevated [Ca 2+] i causes characteristic damage which has been categorized and includes hypercontraction, Z-line damage and myofilament dissolution. The damage closely resembles that described in the isolated mammalian heart and in skeletal muscle preparations when [Ca 2+] i is raised dramatically. 4. 4. Damage can therefore be triggered by releasing Ca 2+ from intracellular sites, as distinct from increasing Ca 2+ entry (as in the Ca 2+-paradox). 5. 5. DNP and ruthenium red also cause identical damage and the results suggest that whilst the fall in pH i associated with ischaemia is probably the consequence of Ca 2+/2H + exchange at the mitochondria, coupled with ATP hydrolysis, lowered pH i by mitochondrial action is probably not the only cause of myofilament dissolution. 6. 6. Damage is not prevented by pretreatment with leupeptin, an inhibitor of Ca 2+-activated neutral proteases, and it is concluded that the latter are probably not implicated in rapid and dramatic damage. 7. 7. The possible involvement of lysosomal enzymes in damage triggered by high [Ca 2+] i is discussed.