Cardiac thin filament regulation and the Frank-Starling mechanism.
The heart has an intrinsic ability to increase systolic force in response to a rise in ventricular filling (the Frank-Starling law of the heart). It is widely accepted that the length dependence of myocardial activation underlies the Frank-Starling law of the heart. Recent advances in muscle physiology have enabled the identification of the factors involved in length-dependent activation, viz., titin (connectin)-based interfilament lattice spacing reduction and thin filament "on-off" regulation, with the former triggering length-dependent activation and the latter determining the number of myosin molecules recruited to thin filaments. Patients with a failing heart have demonstrated reduced exercise tolerance at least in part via depression of the Frank-Starling mechanism. Recent studies revealed that various mutations occur in the thin filament regulatory proteins, such as troponin, in the ventricular muscle of failing hearts, which consequently alter the Frank-Starling mechanism. In this article, we review the molecular mechanisms of length-dependent activation, and the influence of troponin mutations on the phenomenon.
Department of Cell Physiology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Fuyu
F
Kobirumaki-Shimozawa
Takahiro
T
Inoue
Seine A
SA
Shintani
Kotaro
K
Oyama
Takako
T
Terui
Susumu
S
Minamisawa
Shin'ichi
S
Ishiwata
Norio
N
Fukuda
D000818:Animals; D024722:Cardiac Myosins / Q000378:metabolism; D064211:Connectin / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D012518:Sarcomeres / Q000378:metabolism*; D046749:Starlings / Q000502:physiology*; D014336:Troponin / Q000378:metabolism
D064211:Connectin; D014336:Troponin; D024722:Cardiac Myosins