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 (ktr) were determined at different SLs (1.9 and 2.3 μm) in isolated human, murine, and porcine permeabilized cardiomyocytes. ktr 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). ktr was higher (P < 0.05) in mice than in humans or pigs at all Ca2+ concentrations ([Ca2+]) [maximum ktr (ktr,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 ktr did not depend on SL in any species. Moreover, when the ktr values for each species were expressed relative to their respective maxima, similar Ca2+ dependencies were obtained. Ten millimolar Pi decreased force to ∼60-65% and left ΔpCa50 unaltered in all three species. Pi increased ktr,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 ktr, but SL does not appear to modulate the cross-bridge turnover rates in human, murine, and porcine hearts.
|Journal||American Journal of Physiology - Regulatory Integrative and Comparative Physiology|
|Publication status||Published - 1 Jul 2007|