doi: 10.1161/hc3901.095898
(Circulation. 2001;104:1639.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Length Dependence of Tension Generation in Rat Skinned Cardiac Muscle
Role of Titin in the Frank-Starling Mechanism of the Heart
Department of Physiology II (N.F., S.K.), the Jikei University School of Medicine, Tokyo; and the Department of Physics (D.S., S.I.), School of Science and Engineering, the Advanced Research Institute for Science and Engineering (S.I.), and the Materials Research Laboratory for Bioscience and Photonics (S.I.), Waseda University, Tokyo, Japan.
Correspondence to Norio Fukuda, PhD, Department of Physiology II, the Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. E-mail noriof{at}jikei.ac.jp
Background— At the basis of the Frank-Starling mechanism is the intrinsic ability of cardiac muscle to produce active tension in response to stretch. Titin, a giant filamentous molecule involved in passive tension development, is intimately associated with the thick filament in the sarcomere. Titin may therefore contribute to active tension development by modulating the thick filament structure when the muscle is elongated.
Methods and Results— Rat skinned right ventricular trabeculae were used. Passive tension at a sarcomere length (SL) of 2.0 to 2.4 µm was decreased after treatment of the preparation with trypsin (0.25 µg/mL) for 13 minutes in the relaxed state at 20°C. This mild trypsin treatment degraded titin without affecting other major contractile proteins. The sarcomere structure was little affected by brief contractions in the trypsin-treated preparations. When SL was adjusted to the slack SL (1.9 µm), active tension was unaffected by trypsin under partial (pCa 5.55) and maximal (pCa 4.8) activation. At longer SLs, however, active tension was significantly (P<0.01) decreased after trypsin treatment at either pCa. The increase in active tension on reduction of interfilament lattice spacing, produced by dextran T-500 (molecular weight 
500 000), was not influenced by trypsin (SL 1.9 µm). In trypsin-treated preparations, the increase in active tension as a function of muscle diameter was nearly the same for lengthening and osmotic compression at the slack SL.
Conclusions— The length-dependent activation in cardiac muscle, an underlying mechanism of the Frank-Starling law of the heart, is at the myofilament level, predominantly modulated by titin and interfilament lattice spacing changes.
Key Words: myocardial contraction • myocardium • contractility
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