Abstract
Balance between energy supply and demand is finely tuned in heart. In beating heart, intrinsic homeostasis depends on the parallel activation of both modules. Here we used the in vitro approach recently introduced in the Institute (the permeabilized skinned fiber) to study energetics of the four different cardiac chambers (right and left atria, right and left ventricles) in order to evidence local differences in the energetics regulation. Using high-resolution oxygraphy, mitochondrial function was quantified and apparent affinities of mitochondrial respiration for added ADP and ATP were obtained in absence or not of 25μM-blebbistatin (myosin ATPase inhibitor). Measurement of ATP hydrolysis by spectrofluorometry was also experimented in presence or not of blebbistatin after inhibition of mitochondrial oxidative phosphorylation (oligomycin, ATP synthase inhibitor) and respiratory chain inhibitor (rotenone). Apparent affinities of mitochondrial oxidative phosphorylation for ADP were significantly higher in ventricles compared to atria. Presence of blebbistatin induced a significant increase in the affinity in left atrium, underlining the small mitochondrial sensitivity to ADP in the case of myosin ATPase inhibition. Blebbistatin addition under condition of mitochondrial inhibition induced a 50% inhibition of ATP hydrolysis in the left ventricle defining an interesting specific regulation in this compartment. We conclude on the hypothesis of different “channeling” mechanisms between energy supply and energy demand in each cardiac compartments. Our results clearly show a weaker adaptability in energy regulation in the left atrium compared to the left ventricle. A model of failing rat heart is now under study in order to explore the implication of nucleotide adenylic compartimentation on pathological electric instability.
Published Version
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