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(Circulation Research. 2000;86:e1.)
© 2000 American Heart Association, Inc.

UltraRapid Communications

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

Norio Fukuda, Hidetoshi Kajiwara, Shin’ichi Ishiwata, Satoshi Kurihara

From the Department of Physiology (II) (N.F., H.K., S.K.), The Jikei University School of Medicine, Nishishinbashi, Minato-ku, Tokyo, Japan; Department of Physics (S.I.), School of Science and Engineering, Advanced Research Institute for Science and Engineering (S.I.), and Materials Research Laboratory for Bioscience and Photonics (S.I.), Waseda University, Okubo, Shinjuku-ku, Tokyo, Japan.

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 (pCa₅₀) leftward by about 0.2 pCa units. MgADP (0.1, 1, and 5 mmol/L) augmented maximal and submaximal Ca²⁺-activated tension and concomitantly diminished the SL-dependent shift of pCa₅₀ in a concentration-dependent manner. In contrast, pimobendan, a Ca²⁺ sensitizer, which promotes Ca²⁺ binding to troponin C (TnC), exhibited no effect on the SL-dependent shift of pCa₅₀, 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 pCa₅₀ 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 pCa₅₀, 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.

Key Words: MgADP • pimobendan • Ca²⁺ sensitivity • cardiac muscle • sarcomere length

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