Rate of tension redevelopment is not modulated by sarcomere length in permeabilized human, murine, and porcine cardiomyocytes

The increase in Ca²⁺ sensitivity of isometric force development along with sarcomere length (SL) is considered as the basis of the Frank-Starling law of the heart, possibly involving the regulation of crossbridge turnover kinetics. Therefore, the Ca²⁺ dependencies of isometric force production and of the cross-bridge-sensitive rate constant of force redevelopment (k_tr) were determined at different SLs (1.9 and 2.3 μm) in isolated human, murine, and porcine permeabilized cardiomyocytes. k_tr was also determined in the presence of 10 mM inorganic phosphate (Pi), which interfered with the force-generating cross-bridge transitions. The increases in Ca²⁺ sensitivities of force with SL were very similar in human, murine, and porcine cardiomyocytes (ΔpCa₅₀: ∼0.11). k_tr was higher (P < 0.05) in mice than in humans or pigs at all Ca²⁺ concentrations ([Ca²⁺]) [maximum k_tr (k_tr,max) at a SL of 1.9 μm and pCa 4.75: 1.33 ± 0.11, 7.44 ± 0.15, and 1.02 ± 0.05 s^-1, in humans, mice, and pigs, respectively] but k_tr did not depend on SL in any species. Moreover, when the k_tr values for each species were expressed relative to their respective maxima, similar Ca²⁺ dependencies were obtained. Ten millimolar P_i decreased force to ∼60-65% and left ΔpCa₅₀ unaltered in all three species. P_i increased k_tr,max by a factor of ∼1.6 in humans and pigs and by a factor of ∼3 in mice, independent of SL. In conclusion, species differences exert a major influence on k_tr, but SL does not appear to modulate the cross-bridge turnover rates in human, murine, and porcine hearts.