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+].
Highlights
The heart rhythm is maintained by oscillatory changes in [Ca2+]
Spontaneous oscillatory contraction (SPOC) of cardiomyocytes is observed even at constant [ Ca2+] (~ pCa 6) in cardiomyocytes stripped of their membranes and in myofibrils purified from cardiomyocytes[11,12,13,14,15]
These results suggest that cardiomyocytes exhibit oscillatory contraction even at constant [ Ca2+] and that this contraction might be coupled to the physiology of the heartbeat in vivo
Summary
The heart rhythm is maintained by oscillatory changes in [Ca2+]. 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+]. The [ Ca2+] as measured by a calcium indicator (Fluo-4) was the same at 41 °C as in relaxed cells at 36 °C, suggesting that the contraction system of cardiomyocytes is activated at high temperatures even under conditions of very low [ Ca2+]19. This activation has been confirmed in an in vitro motility assay using thin filaments reconstituted with α-tropomyosin and troponin[20]. Adult cardiomyocytes do not show SPOC with temperature jumps, but neonatal cardiomyocytes exhibit oscillatory contraction at high frequencies (6–12 Hz) under conditions of low-frequency C a2+ oscillation (~ 1.4 Hz)[18]. The frequency of sarcomeric oscillations (hyperthermal sarcomeric oscillations, HSOs) is elevated at high temperature but rapidly returns to the original frequency when the temperature is lowered, indicating the reversibility of the change in oscillation frequency[18]
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