Variable crossbridge cycling-ATP coupling accounts for cardiac mechanoenergetics.

Abstract

Cardiac twitch contractions were simulated by Huxley's sliding filament crossbridge muscle model. Huxley's model was extended to include cardiac twitch contractions with a model structure having parallel and series elastic components with a crossbridge contractile element. The appropriate crossbridge energetics were added based on the crossbridge cycling rate and the energy of ATP hydrolysis. The force-length area (FLA) as a measure of the total mechanical energy was computed for both isometric and isotonic contractions in a manner similar to the pressure-volume area (PVA), (Suga, H. Physiol. Rev., 70, 247-277, 1990). Experimental studies have demonstrated that the pressure-volume area (PVA) correlates linearly with cardiac oxygen consumption and hence with the energy expenditure of a cardiac contraction. PVA correlates linearly with cardiac oxygen consumption, and since FLA is analogous to PVA, FLA should correlate with the ATP expended. Simulations comparing FLA with the crossbridge cycling ATP usage showed that at lower muscle fiber activation levels (shorter initial fiber lengths and lower preload levels) FLA decreased more rapidly than the number of muscle fiber crossbridge cycles. This could imply that one ATP can cause more than one crossbridge cycle at lower fiber activation levels as was proposed by Yanagida et al. (Nature, 316, 366-369, 1985). If the number of crossbridge cycles to ATP ratio is allowed to increase at lower activation levels, Huxley's model agrees with the experimental findings on FLA and PVA.