Electrically stimulated in vitro heart cell mimic of acute exercise reveals novel immediate cellular responses to exercise: Reduced contractility and metabolism, but maintained calcium cycling and increased myofilament calcium sensitivity.

Cardiac cellular responses to acute exercise remain undescribed. We present a model for mimicking acute aerobic endurance exercise to freshly isolated cardiomyocytes by evoking exercise‐like contractions over prolonged periods of time with trains of electrical twitch stimulations. We then investigated immediate contractile, Ca2+, and metabolic responses to acute exercise in perfused freshly isolated left ventricular rat cardiomyocytes, after a matrix‐design optimized protocol and induced a mimic for acute aerobic endurance exercise by trains of prolonged field twitch stimulations. Acute exercise decreased cardiomyocyte fractional shortening 50%–80% (p <.01). This was not explained by changes to intracellular Ca2+ handling (p >.05); rather, we observed a weak insignificant Ca2+ transient increase (p =.11), while myofilament Ca2+ sensitivity increased 20%–70% (p <.05). Acidic pH 6.8 decreased fractional shortening 20%–70% (p <.05) because of 20%–30% decreased Ca2+ transients (p <.05), but no difference occurred between control and acute exercise (p >.05). Addition of 1 or 10 mM La− increased fractional shortening in control (1 mM La−: no difference, p >.05; 10 mM La−: 20%–30%, p <.05) and acute exercise (1 mM La−: 40%–90%, p <.01; 10 mM La−: 50%–100%, p <.01) and rendered acute exercise indifferent from control (p >.05). Intrinsic autofluorescence showed a resting NADstate of 0.59 ± 0.04 and FADstate of 0.17 ± 0.03, while acute exercise decreased NADH/FAD ratio 8% (p <.01), indicating intracellular oxidation. In conclusion, we show a novel approach for studying immediate acute cardiomyocyte responses to aerobic endurance exercise. We find that acute exercise in cardiomyocytes decreases contraction, but Ca2+ handling and myofilament Ca2+ sensitivity compensate for this, while acidosis and reduced energy substrate and mitochondrial ATP generation explain this. Significance statement: Endurance exercise is taxing to the heart and it leads to cardiac exhaustion and fatigue with contractile impairment. However, a mechanism for this has not yet been found, at least partly because this has been impossible to study in heart muscle cells (cardiomyocytes, where contraction occurs) since the process of ascertaining cells after physical exercise in and of itself uncouples the exercise effect. We took a different approach and came up with a novel protocol; instead of exercising animals and then preparing cells, we first prepared cells and then supplied exercise to the cell. This showed that the reduced contractile function during and immediately after exercise was caused by acidosis and metabolic impairments, while Ca2+ lessened the dys‐contraction. [ABSTRACT FROM AUTHOR]