LAUSR

The heart transforms the chemical-mechanical reaction of myosin molecules, which move only stochastically by itself, into a robust heartbeat rhythm by its hierarchical structure (Figure 1A, Ishiwata et al., 2017). Myocardial pulsation is thought to be regulated by changes in calcium concentration in cardiomyocytes triggered by electrical excitement from cardiac pacemaker cells (Eisner et al., 2017). However, on the other hand, it has also been found that the heartbeat frequency is too high to sufficiently reduce the calcium concentration in cardiomyocytes that has increased due to muscle contraction (Eisner et al., 2017). The myocardium is known to be contracted when the intracellular calcium concentration is high (Eisner et al., 2017). So why can the heart relax quickly in the early diastole of each heartbeat, even though the calcium concentration in cardiomyocytes is high and the left ventricular pressure is low? Since the left ventricular pressure is low, there is little force to pull and lengthen the sarcomere. And since the calcium concentration in cardiomyocytes is still high, sarcomere generates force. Despite this, the reason why rapid relaxation to fill the ventricle with blood throughout diastole is possible may be that sarcomere has the property of periodically and rapidly relaxing and dilating even if the calcium concentration is still high. In recent years, we have discovered that sarcomere in cardiomyocytes warmed to body temperature becomes an oscillation state that repeats contraction and relaxation (Figure 1B, Shintani et al., 2015). We named the sarcomere oscillations manifested by the heat of this body temperature HSOs (Hyperthermal Sarcomeric Oscillations). We believe that HSOs are the key to answering the previous question. Experiments with isolated cardiomyocytes have shown that HSOs enable rapid lengthening of sarcomere even at high intracellular calcium concentrations, and that the HSOs cycle is close to the heartbeat cycle (Figure 1C, Shintani et al., 2020). Given the rapid lengthening seen in HSOs during diastole of the heart, it explains the rapid lengthening of the heart despite high cardiomyocyte calcium levels and low left ventricular pressure. HSOs are observed at 37°C–43°C in cardiomyocytes where calcium concentration fluctuates at about 1 Hz (Shintani et al., 2015; Shintani et al., 2020). Inhibiting calcium concentration fluctuations narrowed the temperature at which HSOs can be observed to 38°C–43°C (Shintani et al., 2015). To put it very simply, this may be due to a decrease in base calcium concentration. Conversely, when calcium concentration fluctuations higher than 1 Hz, such as heartbeat, occur, the base calcium concentration increases (Eisner et al., 2017), and theminimum temperature required to induce HSOs is likely to be lower than 37°C. The core body temperature of the working heart is higher than other parts of the body. Since even a mere core body temperature is measured at 37–38°C (Yoda et al., 2000), it is highly possible that the HSOs characteristics of sarcomere are manifested at the core body temperature of the working heart, which is considered to be higher. Edited by: Henk Granzier, University of Arizona, United States