KINETIC-STUDIES ON THE BIOLOGICAL-ACTIVITY OF CALMODULIN IN CANINE HEART AND LIVER DURING ENDOTOXIN-SHOCK

Effects of endotoxin administration on the biological activity of calmodulin isolated from canine heart and liver were studied. Calmodulin was isolated and purified to homogeneity. The biological activity of calmodulin was determined by its ability to activate Ca2+-dependent phosphodiesterase. Results obtained 4 h after endotoxin administration show that the V(max) and A0.5 for calmodulin, the V(max) and K(m) for cAMP, and the V(max) and the Hill coefficient for Ca2+ were unchanged, while the S0.5 for Ca2+ for the activation of phosphodiesterase were significantly increased in the heart. The kinetic parameters as described above were not significantly altered in the liver. These data indicate that the biological activity of calmodulin is inhibited in the heart during endotoxin shock and that the nature of inhibition is associated with a mechanism involving a decrease in the affinity (1/S0.5) towards Ca2+ binding. Since calmodulin plays an important role in the regulation of cardiac function through calmodulin-dependent calcium transport systems, our findings may have a pathophysiological significance in contributing to the understanding of myocardial dysfunction in endotoxin shock.