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.

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Nanoscale imaging of cultured cardiomyocytes allows the quantitative assessment of changes in the length of single sarcomeres during contractile events.

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Muscle fiber contraction involves chemical reactions and structural changes that are sensitive to temperature. Ishii et al. show that rapid heating causes cardiac thin filament sliding, and the data could indicate that thin filaments are partially activated during diastole at mammalian body temperature.

Rapid sarcomere lengthening waves propagate along a single muscle myofibril during spontaneous oscillatory contraction (SPOC). In asynchronous insect flight muscles, SPOC is thought to be almost completely synchronized over the entire myofibril. This phenomenon does not require Ca 2+ regulation of the dynamics of the motor proteins, and cannot be explained simply by the longitudinal mechanical equilibrium among sarcomeres in the myofibril. In the present study, we rationalize these phenomena by considering the lateral mechanical equilibrium, in which two tensions originating from the inverse relationship between sarcomere length and lattice spacing, along with the lattice alignment, play important roles in the mechanical communication between motor proteins on adjacent filaments via the Z-disc. The proposed model is capable of explaining various SPOC phenomena based on the stochastic power-stroke mechanism of motor proteins, which responds to temporal changes in longitudinal mechanical load.

The main problem of orthopedic and dental titanium (Ti) implants has been poor bone-bonding to the metal. Various coatings to improve the bone-bonding, including the hydroxyapatite and titania, have been developed, and some of them have been to successfully applied clinical use. On the other hand, there are still challenges to provide antibacterial activity and promotion of bone growth on Ti. It was shown that a calcium-deficient calcium titanate coating on Ti and its alloys exhibits high bone-bonding owing to its apatite formation. In this study, Sr and Ag ions, known for their promotion of bone growth and antibacterial activity, were introduced into the calcium-deficient calcium titanate by a three-step aqueous solution treatment combined with heat. The treated metal formed apatite within 3 days in a simulated body fluid and exhibited antibacterial activity to Escherichia coli without showing any cytotoxicity in MC3T3-E1 preosteoblast cells. Furthermore, the metal slowly released 1.29 ppm of Sr ions. The Ti with calcium-deficient calcium titanate doped with Sr and Ag will be useful for orthopedic and dental implants, since it should bond to bone because of its apatite formation, promote bone growth due to Sr ion release, and prevent infection owing to its antibacterial activity.

The heart rhythm is maintained by oscillatory changes in [Ca2+]. However, it has been suggested that the rapid drop in blood pressure that occurs with a slow decrease in [Ca2+] preceding early diastolic filling is related to the mechanism of rapid sarcomere lengthening associated with spontaneous tension oscillation at constant intermediate [Ca2+]. Here, we analyzed a new type of oscillation called hyperthermal sarcomeric oscillation. Sarcomeres in rat neonatal cardiomyocytes that were warmed at 38–42 °C oscillated at both slow (~ 1.4 Hz), Ca2+-dependent frequencies and fast (~ 7 Hz), Ca2+-independent frequencies. Our high-precision experimental observations revealed that the fast sarcomeric oscillation had high and low peak-to-peak amplitude at low and high [Ca2+], respectively; nevertheless, the oscillation period remained constant. Our numerical simulations suggest that the regular and fast rthythm is maintained by the unchanged cooperative binding behavior of myosin molecules during slow oscillatory changes in [Ca2+].