Myocardial stunning is a form of reversible myocardial ischemia/reperfusion injury associated with systolic and diastolic contractile dysfunction. In the isolated rat heart model, myocardial stunning is characterized by specific C-terminal proteolysis of the myofilament protein, troponin I (cTnI) that yields cTnI . To determine the effect of this particular C-terminal truncation of cTnI, without the confounding factor of other stunning-induced protein modifications, a series of solution

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... cal assays has been undertaken using the human homologue of mouse/rat cTnI 1-193 , cTnI . Affinity chromatography and actin sedimentation experiments detected little, or no, difference between the binding of cTnI (cTnI 1-209 ) and cTnI to actin-tropomyosin, troponin T, or troponin C. Both cTnI and cTnI 1-192 inhibit the actin-tropomyosin-activated ATPase activity of myosin subfragment 1 (S1), and this inhibition is released by troponin C in the presence of Ca 2ϩ . However, cTnI 1-192 , when reconstituted as part of the troponin complex (cTn 1-192 ), caused a 54Ϯ11% increase in the maximum Ca 2ϩ -activated actin-tropomyosin-S1 ATPase activity, compared with troponin reconstituted with cTnI (cTn). Furthermore, cTn 1-192 increased Ca 2ϩ sensitivity of both the actin-tropomyosinactivated S1 ATPase activity and the Ca 2ϩ -dependent sliding velocity of reconstituted thin filaments, in an in vitro motility assay, compared with cTn. In an in vitro force assay, the actin-tropomyosin filaments bearing cTn 1-192 developed only 76Ϯ4% (PϽ0.001) of the force obtained with filaments composed of reconstituted cTn. We suggest that cTnI proteolysis may contribute to the pathophysiology of myocardial stunning by altering the Ca 2ϩ -sensing and chemomechanical properties of the myofilaments. (Circ Res. 2003;93:917-924.)