Troponin and titin coordinately regulate length-dependent activation in skinned porcine ventricular muscle.
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.
Terui
Takako
T
Department of Cell Physiology, The Jikei University School of Medicine, Tokyo 105-8461, Japan. pu-cha@jikei.ac.jp
Sodnomtseren
Munguntsetseg
M
Matsuba
Douchi
D
Udaka
Jun
J
Ishiwata
Shin'ichi
S
Ohtsuki
Iwao
I
Kurihara
Satoshi
S
Fukuda
Norio
N
D000818:Animals; D064211:Connectin; D066298:In Vitro Techniques; D007700:Kinetics; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D013552:Swine; D019209:Troponin C / Q000378:metabolism*; D016276:Ventricular Function
D064211:Connectin; D009124:Muscle Proteins; D019209:Troponin C; D011494:Protein Kinases