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Regulation of Cardiac Muscle Contraction

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

István Ferenc Édes,¹ Dániel Czuriga,¹ Gábor Csányi,² Stefan Chopicki,² Fabio A. Recchia,^3,4 Attila Borbély,¹ Zoltán Galajda,¹ István Édes,¹ Jolanda van der Velden,⁵ Ger J. M. Stienen,⁵ and Zoltán Papp¹

¹Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Debrecen, Hungary; ²Department of Experimental Pharmacology, Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland; ³Sector of Medicine, Scuola Superiore Sant’ Anna, Pisa, Italy; ⁴New York Medical College, Valhalla, New York; and ⁵Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands

Submitted 27 July 2006 ; accepted in final form 13 November 2006

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 cross-bridge 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 (P_i), 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 (pCa₅₀: 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 pCa₅₀ 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.

mouse; pig; heart; skinned muscle; myofilament length-dependent activation; rate of tension redevelopment; calcium

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				K. S. McDonald Regulation of cardiac muscle contraction: how paramount are the sarcomeres? Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R961 - R962. [Full Text] [PDF]