The Journal of General Physiology
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Published online February 25, 2008
doi:10.1085/jgp.200709895
The Journal of General Physiology, Vol. 131, No. 3, 275-283
The Rockefeller University Press, 0022-1295 $30.00
© 2008 Terui et al.
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ARTICLE

 Troponin and Titin Coordinately Regulate Length-dependent Activation in Skinned Porcine Ventricular Muscle



Takako Terui1, Munguntsetseg Sodnomtseren1,2, Douchi Matsuba1, Jun Udaka1, Shin'ichi Ishiwata2, Iwao Ohtsuki1, Satoshi Kurihara1, and Norio Fukuda1

1 Department of Cell Physiology, The Jikei University School of Medicine, Tokyo 105-8461, Japan
2 Department of Physics, Waseda University, Tokyo 169-8555, Japan

Correspondence to Norio Fukuda: noriof{at}jikei.ac.jp; or Takako Terui: pu-cha{at}jikei.ac.jp

We investigated the molecular mechanism by which troponin (Tn) regulates the Frank-Starling mechanism of the heart. Quasi-complete reconstitution of thin filaments with rabbit fast skeletal Tn (sTn) attenuated length-dependent activation in skinned porcine left ventricular muscle, to a magnitude similar to that observed in rabbit fast skeletal muscle. The rate of force redevelopment increased upon sTn reconstitution at submaximal levels, coupled with an increase in Ca2+ sensitivity of force, suggesting the acceleration of cross-bridge formation and, accordingly, a reduction in the fraction of resting cross-bridges that can potentially produce additional active force. An increase in titin-based passive force, induced by manipulating the prehistory of stretch, enhanced length-dependent activation, in both control and sTn-reconstituted muscles. Furthermore, reconstitution of rabbit fast skeletal muscle with porcine left ventricular Tn enhanced length-dependent activation, accompanied by a decrease in Ca2+ sensitivity of force. These findings demonstrate that Tn plays an important role in the Frank-Starling mechanism of the heart via on–off switching of the thin filament state, in concert with titin-based regulation.

Abbreviations used in this paper: BDM, 2,3-butanedione monoxime; PLV, porcine left ventricular muscle; SL, sarcomere length; Tn, troponin.


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