Stretch of Contracting Cardiac Muscle Abruptly Decreases the Rate of Phosphate Release at High and Low Calcium

Background: Phosphate is released by the cardiac actomyosin ATPase during contraction.Results: Stretching active cardiac muscle decreases phosphate release within milliseconds.Conclusion: Mechanical stimuli such as stretch cause an immediate change in actomyosin ATPase kinetics.Significance: Stretch facilitates a powerful contraction by increasing cross-bridges in a pre-power stroke state, and changes cytoplasmic phosphate flux, which may influence energetic homeostasis.The contractile performance of the heart is linked to the energy that is available to it. Yet, the heart needs to respond quickly to changing demands. During diastole, the heart fills with blood and the heart chambers expand. Upon activation, contraction of cardiac muscle expels blood into the circulation. Early in systole, parts of the left ventricle are being stretched by incoming blood, before contraction causes shrinking of the ventricle. We explore here the effect of stretch of contracting permeabilized cardiac trabeculae of the rat on the rate of inorganic phosphate (Pi) release resulting from ATP hydrolysis, using a fluorescent sensor for Pi with millisecond time resolution. Stretch immediately reduces the rate of Pi release, an effect observed both at full calcium activation (32 μmol/liter of Ca2+), and at a physiological activation level of 1 μmol/liter of Ca2+. The results suggest that stretch redistributes the actomyosin cross-bridges toward their Pi-containing state. The redistribution means that a greater fraction of cross-bridges will be poised to rapidly produce a force-generating transition and movement, compared with cross-bridges that have not been subjected to stretch. At the same time stretch modifies the Pi balance in the cytoplasm, which may act as a cytoplasmic signal for energy turnover. Background: Phosphate is released by the cardiac actomyosin ATPase during contraction. Results: Stretching active cardiac muscle decreases phosphate release within milliseconds. Conclusion: Mechanical stimuli such as stretch cause an immediate change in actomyosin ATPase kinetics. Significance: Stretch facilitates a powerful contraction by increasing cross-bridges in a pre-power stroke state, and changes cytoplasmic phosphate flux, which may influence energetic homeostasis. The contractile performance of the heart is linked to the energy that is available to it. Yet, the heart needs to respond quickly to changing demands. During diastole, the heart fills with blood and the heart chambers expand. Upon activation, contraction of cardiac muscle expels blood into the circulation. Early in systole, parts of the left ventricle are being stretched by incoming blood, before contraction causes shrinking of the ventricle. We explore here the effect of stretch of contracting permeabilized cardiac trabeculae of the rat on the rate of inorganic phosphate (Pi) release resulting from ATP hydrolysis, using a fluorescent sensor for Pi with millisecond time resolution. Stretch immediately reduces the rate of Pi release, an effect observed both at full calcium activation (32 μmol/liter of Ca2+), and at a physiological activation level of 1 μmol/liter of Ca2+. The results suggest that stretch redistributes the actomyosin cross-bridges toward their Pi-containing state. The redistribution means that a greater fraction of cross-bridges will be poised to rapidly produce a force-generating transition and movement, compared with cross-bridges that have not been subjected to stretch. At the same time stretch modifies the Pi balance in the cytoplasm, which may act as a cytoplasmic signal for energy turnover.