Mechanoenergetic estimation of multiple cross-bridge steps per ATP in a beating heart

Abstract

The efficiency from the ventricular O2 consumption (VO 2) to the total mechanical energy (TME) generated by ventricular contraction has proved relatively constant at ∼35%, independent of the loading and contractile conditions in a canine heart. TME is the sum of the external mechanical work for ejecting a stroke volume against the afterload and of the mechanical potential energy for developing ventricular pressure in each beat. The ∼35% VO2-to-TME efficiency indicates an also constant ∼60% ATP-to-TME efficiency in a beating heart, based on the nominal ∼60% VO2-to-ATP efficiency in the myocardial oxidative phosphorylation. I newly attempted to explain the load-independent ∼60% ATP-to-TME efficiency by the recently reported ∼7-10 nm unitary step size and ∼0.8-1.5 pN unitary force of a cross-bridge (CB) at the molecular level in in vitro motility assays. This single CB behavior suggests that its unitary cycle could generate a mechanical energy of ∼0.6-1.5 × 10-20 J at most. From the nominal free energy of ∼10×10-20 J per ATP, the efficiency from one ATP to the CB unitary cycle would then be ∼6-15%. This low efficiency is only ∼1/10-1/4 of the ∼60% ATP-to-TME efficiency at the heart level. This discrepancy suggests that each CB would repeat the unitary cycle at least ∼4-10 times per ATP to achieve the high constant ATP-to-TME efficiency in a beating heart. This seems to represent a considerable mechanoenergetic advantage of the heart at the integrative heart level as compared to the molecular CB level.