Comparative studies on the role of calcium in triggering subcellular damage in cardiac muscle.
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 [Ca2+]i in promoting severe damage. A23187 and caffeine are believed to cause a rise in [Ca2+]i. Elevated [Ca2+]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 [Ca2+]i is raised dramatically. Damage can therefore be triggered by releasing Ca2+ from intracellular sites, as distinct from increasing Ca2+ entry (as in the Ca2+-paradox). DNP and ruthenium red also cause identical damage and the results suggest that whilst the fall in pHi associated with ischaemia is probably the consequence of Ca2+/2H+ exchange at the mitochondria, coupled with ATP hydrolysis, lowered pHi by mitochondrial action is probably not the only cause of myofilament dissolution. Damage is not prevented by pretreatment with leupeptin, an inhibitor of Ca2+-activated neutral proteases, and it is concluded that the latter are probably not implicated in rapid and dramatic damage. The possible involvement of lysosomal enzymes in damage triggered by high [Ca2+]i is discussed.
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D004140:Dinitrophenols / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008929:Mitochondria, Heart / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000648:ultrastructure*; D011896:Rana temporaria; D012430:Ruthenium Red; D013347:Subcellular Fractions / Q000502:physiology*
D004140:Dinitrophenols; D007976:Leupeptins; D012430:Ruthenium Red; D000001:Calcimycin; D002110:Caffeine; C032854:leupeptin; D002118:Calcium