Effects of MgADP on Length Dependence of Tension Generation in Skinned Rat Cardiac Muscle

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Abstract
—The effect of MgADP on the sarcomere length (SL) dependence of tension generation was investigated using skinned rat ventricular trabeculae. Increasing SL from 1.9 to 2.3 μm decreased the muscle width by ≈11% and shifted the midpoint of the pCa-tension relationship (pCa 50 ) leftward by about 0.2 pCa units. MgADP (0.1, 1, and 5 mmol/L) augmented maximal and submaximal Ca 2+ -activated tension and concomitantly diminished the SL-dependent shift of pCa 50 in a concentration-dependent manner. In contrast, pimobendan, a Ca 2+ sensitizer, which promotes Ca 2+ binding to troponin C (TnC), exhibited no effect on the SL-dependent shift of pCa 50 , suggesting that TnC does not participate in the modulation of SL-dependent tension generation by MgADP. At a SL of 1.9 μm, osmotic compression, produced by 5% wt/vol dextran (molecular weight ≈464 000), reduced the muscle width by ≈13% and shifted pCa 50 leftward to a similar degree as that observed when increasing SL to 2.3 μm. This favors the idea that a decrease in the interfilament lattice spacing is the primary mechanism for SL-dependent tension generation. MgADP (5 mmol/L) markedly attenuated the dextran-induced shift of pCa 50 , and the degree of attenuation was similar to that observed in a study of varying SL. The actomyosin-ADP complex (AM.ADP) induced by exogenous MgADP has been reported to cooperatively promote myosin attachment to the thin filament. We hereby conclude that the increase in the number of force-generating crossbridges on a decrease in the lattice spacing is masked by the cooperative effect of AM.ADP, resulting in depressed SL-dependent tension generation. The full text of this article is available at http://www.circresaha.org.