Changes in creatine kinase M localization in acute ischemic myocardial cells. Immunoelectron microscopic studies.

Abstract

To clarify the changes in creatine kinase M localization along with the progress of myocardial ischemia, immunoelectron microscopic studies were performed using rabbit anti-canine creatine kinase M Fab'-horseradish peroxidase conjugate in 21 dogs. Myocardial ischemia was induced by occlusion of the left anterior descending coronary artery for 15 (n = 5), 30 (n = 5), 60 (n = 5), or 180 (n = 4) minutes. Two dogs were used as normal controls. As we have already demonstrated, most creatine kinase M in normal myocardial cells was localized over the entire A band in association with the thick filament, suggesting that creatine kinase in this region (A-band creatine kinase) was the enzyme coupled with myosin ATPase. After 15 minutes of ischemia, creatine kinase M showed only minimal changes in its location, indicating that A-band creatine kinase still has the ability to couple with myosin ATPase (reversible injury). However, after 30 minutes of ischemia, A-band creatine kinase diffused markedly to the I band (transitional phase), and after 60 minutes of ischemia, it leaked out to extracellular spaces (irreversible injury). After 180 minutes of ischemia, most A-band creatine kinase disappeared from the myocardial cells (coagulation necrosis). These features of creatine kinase M localization seemed to reflect each stage of ischemic cell injury. We conclude that myocardial ischemia results in a dissociation of creatine kinase molecules from the thick filament, which leads the energy transport system to destruction.

Mobility of creatine phosphokinase and beta-enolase in cultured muscle cells

“…One may note that upon induction of a contraction, the mobility of this fraction of CK is increased to a value near that of ,B-enolase. This observation is comparable to that of Otsu et al (1993), who noticed that in heart, CK is localized in the A-band, whereas after ischemia this enzyme is more dispersed in the sarcomeres.…”

“…The MM-CK is cytosolic; a small fraction of this enzyme is bound specifically to the M-line structure of the sarcomeres (Wallimann and Eppenberger, 1985), and another fraction seems to be loosely bound to other sites in the sarcomeres. The exact localization of this loosely bound MM-CK is controversial, as Otsu et al (1989as Otsu et al ( , 1993 observed a localization in the whole A-band, whereas Wegmann et al (1992) observed this isoform both localized at the M-line and highly confined to the I-band.…”

Protective Effect of L-Arginine in Experimentally Induced Myocardial Ischemia: Comparison With Aspirin

“…Like cTnI, CK-MB is a well-known marker for MI; it is even more specific to cardiac muscle than to skeletal muscle. 38 Low-density lipoprotein oxidizability was increased, but not to the level of statistical significance, after the induction of hypercholesterolemia and MI. Hypercholesterolemia is associated with increased production of ROS and increased oxidation of LDL cholesterol.…”

Myofibrillar disruption in hypocontractile myocardium showing perfusion-contraction matches and mismatches

“…Although marked reductions in total CK activity reduce myocardial contractile reserve (22,31), normal resting levels of function can be maintained in the face of substantial reductions in total CK (31). At the myofibrillar level, microcompartmentation of CK may play an important role in its functional coupling to myofibrillar ATPase (22,27,42,47). Additional issues relate to possible reductions in the activity of normally functional myofibrillar CK due to limited substrate (ADP) availability (19) and to effects of flow reduction on other myofibrillar components (15).…”