The velocity of cardiac sarcomere shortening: mechanisms and implications

Abstract

A classical paper published by Michael Barany almost 50 years ago demonstrated a tight correlation between the mechanical parameter of maximal velocity of shortening and the biochemical parameter of myosin ATPase activity in a wide spectrum of species. Here, we review the determinants of muscle dynamics by mechanical load and the relation between sarcomere shortening velocity and cross-bridge dynamics in rat myocardium containing a range of fast and slow myosin. Observations from molecular level to mechanics of the intact human heart suggest that cardiac actin-myosin kinetic properties are matched so as to optimize myocardial strain rate and allow for the maximum rate of hydraulic energy output observed during ejection in the whole ventricle.

Figure 1

Isolated rat right ventricular endocardial trabecula attached to a high-speed motor via a hook inserted through a remnant of the tricuspid valve on the right hand side, and a block of free wall ventricular tissue held within a platinum basket attached to a sensitive force transducer on the left hand side. The small axial dimensions (<200 μm wide and <100 μm thin) of these ultra-thin myocardial preparations both ensure adequate oxygenation and waste product removal as well as allow for the measurement of high-speed sarcomere length by laser diffraction techniques; longitudinal uniformity (2–5 mm in length) allow for unambiguous sarcomere mechanics measurement under strict sarcomere length feedback control.

Figure 2

Force-sarcomere velocity relationships (left panel) and Force-Power relationships (right panel) determined in isolated rat myocardium composed of predominantly α myosin (solid lines) or β myosin (dashed lines). Expression of the slower β myosin results in reduced sarcomere shortening velocity at all mechanical loads as well as reduced power development. Maximum power is generated at ~30% F_max as indicated by the vertical dotted line. Modified from (de Tombe and ter Keurs, 1991a).

Figure 3

Average single cross bridge Force-sarcomere velocity relationships (left panel) and Force-Power relationships (right panel) prediction based on measurement of sarcomere stiffness during sarcomere shortening for α myosin (solid lines) or β myosin (dashed lines). The attached cycling cross bridges behave mechanically as a visco-elastic unit, where shortening velocity is linearly inversely proportional to muscle load. Maximum power at the single cross bridge level is generated at 50% F_max as indicated by the vertical dotted line. Modified from (de Tombe and ter Keurs, 1992; de Tombe and ter Keurs, 1991a; ter Keurs et al., 2010).

Figure 4

Relationship between muscle stiffness and sarcomere shortening velocity. The predicted relationship (solid line) is given by K = f/(g_o + g₁•V); the dotted line indicates experimentally measured sarcomere stiffness. Since muscle stiffness is proportional to the number of attached cycling cross bridges, these data indicate that the number of attached cross-bridges declines (to ~12%) during maximal unloaded sarcomere shortening; a reduced number of cross bridges as function of sarcomere shortening causes the curved, hyperbolic force-sarcomere velocity relationship seen in muscle (cf. figure 2). Modified from (Landesberg et al., 2004; de Tombe and ter Keurs, 1992).

Figure 5

Treatment of rats with propyl-thiouracil (PTU) induces hypothyroidism that leads to the gradual replacement over several weeks of α- by β-myosin (MHC) in the heart (top panel). There is a direct proportional relationship between the myosin composition and various mechano-energetic parameters such as the ATPase activity during maximum isometric force development (ATPase_max), the ratio of ATPase activity and force development (tension-cost), the rate of force redevelopment following a sarcomere length perturbation (k_tr), and the maximum unloaded velocity of sarcomere shortening (V_SLmax). Modified from (de Tombe and ter Keurs, 1991a; Rundell et al., 2005). The 100% level of the various parameters is indicated by the solid hexagonal: ATPase_max = 600 pmol/s; tension-cost = 10 pmol/s/mm³; K_tr = 16/s; V_SLmax = 15 μm/s.

Figure 6

Temperature dependence of mechano-energetic parameters in the form of an Arrhenius plot measured in euthyroid isolated rat myocardium; equivalent temperatures in °C are indicated above the abscissa. Temperature strongly affects all parameters (average Q10 = ~ 4; T indicates absolute temperature in K). Modified from (de Tombe and ter Keurs, 1990b; de Tombe and Stienen, 2007). The 100% level of the various parameters is indicated by the solid hexagonal: ATPase_max = 800 pmol/s; tension-cost = 18 pmol/s/mm³; K_tr = 50/s; V_SLmax = 25 μm/s.