Diminished Ca2+ Sensitivity of Skinned Cardiac Muscle Contractility Coincident With Troponin T–Band Shifts in the Diabetic Rat

Abstract We have measured the apparent Ca2+ sensitivities of force development in skinned cardiac trabeculae at different sarcomere lengths together with shifts in troponin (Tn) T subunits on specimens from the same hearts and drawn insights into the pathogenesis of myocardial dysfunction in the diabetic rat. The Ca2+-force relations were measured at a long (2.4-μm) and a short (1.9-μm) sarcomere length. In disease, compared with the control condition, the apparent Ca2+ sensitivity was greatly diminished at a sarcomere length of 1.9 μm but not affected at all at the long length (2.4 μm). We also examined the alterations in contractile regulatory proteins TnT and TnI by both sodium dodecyl sulfate–polyacrylamide gel electrophoresis and Western blots. The TnI band was largely unperturbed, but major changes were discerned in TnT. The normal rat heart indicated two major bands (TnT1 and TnT2) and a faint third band (TnT3); in the diabetic rat heart, there was a significant shift in intensity from TnT1 to TnT3...