Effects of diabetes on isometric tension as a function of [Ca2+] and pH in rat skinned cardiac myocytes.

In diabetes a primary myocardial defect occurs that is characterized by decreases in systolic pressure and cardiac output. The present study investigates whether diabetes causes a decreased maximum tension-generating ability, decreased Ca2+ sensitivity of myofilaments, or no change in cardiac myofilament contractile properties at pH 7.0 and 6.6. Hearts from Wistar rats were excised and mechanically disrupted 6-10 wk after injection of streptozotocin. The resulting myocyte-size preparations of skinned myocardium were used to determine the steady-state tension-negative, log molar Ca2+ concentration (pCa) relation. Maximum tension was unchanged, and the pCa of half-maximum tension generation was 0.14 pCa units lower than control for skinned myocytes from diabetic rats at pH 7.0. A significantly lower than normal maximum tension was observed at pH 6.6 for cardiac myocytes from diabetic rats. Increased expression of beta-myosin heavy chain (MHC) occurred in hearts from diabetic rats. Two troponin T (TnT) isoforms in myocardium of adult rats were identified by Western blots. The ratio of the two TnT isoforms were altered in diabetes. Changes in cardiac MHC and TnT expression may contribute to the observed decrease in Ca2+ sensitivity of myofilaments at pH 7.0 and decreased maximum tension-generating ability at pH 6.6 in diabetes.