Mechanism of contraction rhythm homeostasis for hyperthermal sarcomeric oscillations of neonatal cardiomyocytes

Abstract

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+].

Effects of high-pressure treatment on the structure and function of myofibrils

“…In a previous study, we found that in living cardiomyocytes, warming to a temperature close to body temperature can manifest sarcomeric oscillations [ 28 , 29 ]. Then, from a mathematical model that reproduces that phenomenon, it was estimated that warming the myofibrils could put the myofibrils into a sarcomeric oscillation state [ 29 , 31 , 32 ]. This time, we cannot say whether the mechanism is exactly the same as this estimation, but we succeeded in putting the myofibrils, which are no longer in the sarcomeric oscillation state at 25°C, into the sarcomeric oscillation state by warming them to 35°C.…”

“…1 d, e). The peak frequency became unsharp, and the periodic stability decreased due to the widening of the filament lattice spacing, the spatial limitation of the interaction between myosin and actin filaments, and the low probability of crossbridge formation [ 29 , 31 , 33 – 36 ]. The shortening of the A band, or myosin filament, reinforced this tendency by reducing the number of myosins that could form crossbridges ( Fig.…”

“…This was probably because the activation of myosin movement by increasing the temperature increased the number of myosins forming crossbridges [ 28 , 29 , 37 , 38 ]. It is considered that the probability of crossbridge formation was also increased because troponin and tropomyosin became less likely to inhibit myosin crossbridge formation due to thermal fluctuation [ 28 , 29 , 37 , 38 ]. In addition, the thermal fluctuation of the actin filament itself may have increased the probability of proximity to the myosin head and increased the probability of crossbridge formation.…”

“…The data from the optical microscope were subjected to Gaussian filter processing ( ) to remove image noise. The sarcomere length was measured with subpixel accuracy by estimating the peak position of the brightness distribution corresponding to the I band by fitting it to a parabolic function with respect to the brightness distribution acquired in the contraction-axis direction of the myofibrils [ 27 – 29 , 31 ]. The length and width of the A band were measured by estimating the inflection point of the luminance distribution.…”

“…Then, in order to evaluate the contractile function of myofibrils treated with high pressure, sarcomeric oscillation was induced and observed. Sarcomeric oscillation is a phenomenon in which sarcomere repeatedly contracts and relaxes [21][22][23][24][25][26][27][28][29]. It has been reported that myofibrils immersed in a solution that causes sarcomere to contract moderately are in a sarcomeric oscillation state even though there is no change in the calcium concentration of the solution.…”